Brief Communications

  • Brief Communication |

    The long noncoding RNA SCHLAP1 has been reported to act by depleting the SWI/SNF complex from genomic sites, but new data show that SWI/SNF remains localized to chromatin in the presence of SCHLAP1, suggesting that SCHLAP1 may act independently of SWI/SNF.

    • Jesse R. Raab
    • , Keriayn N. Smith
    • , Camarie C. Spear
    • , Carl J. Manner
    • , J. Mauro Calabrese
    •  & Terry Magnuson
  • Brief Communication |

    In vivo analysis of pairwise combinations of tumor suppressor losses using a barcode-based assay in mice identifies unpredicted genetic interactions and shows that the effects of tumor suppressor alterations can be context-dependent.

    • Zoë N. Rogers
    • , Christopher D. McFarland
    • , Ian P. Winters
    • , Jose A. Seoane
    • , Jennifer J. Brady
    • , Stephanie Yoon
    • , Christina Curtis
    • , Dmitri A. Petrov
    •  & Monte M. Winslow
  • Brief Communication |

    The clinical phenotype associated with BRD4 haploinsufficiency overlaps with Cornelia de Lange syndrome, which is often caused by mutations in NIPBL. The authors show that BRD4 and NIPBL physically interact and co-bind at super-enhancers.

    • Gabrielle Olley
    • , Morad Ansari
    • , Hemant Bengani
    • , Graeme R. Grimes
    • , James Rhodes
    • , Alex von Kriegsheim
    • , Ana Blatnik
    • , Fiona J. Stewart
    • , Emma Wakeling
    • , Nicola Carroll
    • , Alison Ross
    • , Soo-Mi Park
    • , Wendy A. Bickmore
    • , Madapura M. Pradeepa
    •  & David R. FitzPatrick
  • Brief Communication |

    Individuals from a Greenlandic Inuit population with homozygous loss-of-function variants in ADCY3 (adenylate cyclase 3) have increased risk for obesity and type 2 diabetes. Carriers of rare ADCY3 variants in trans-ancestry populations also show increased association with type 2 diabetes.

    • Niels Grarup
    • , Ida Moltke
    • , Mette K. Andersen
    • , Maria Dalby
    • , Kristoffer Vitting-Seerup
    • , Timo Kern
    • , Yuvaraj Mahendran
    • , Emil Jørsboe
    • , Christina V. L. Larsen
    • , Inger K. Dahl-Petersen
    • , Arthur Gilly
    • , Daniel Suveges
    • , George Dedoussis
    • , Eleftheria Zeggini
    • , Oluf Pedersen
    • , Robin Andersson
    • , Peter Bjerregaard
    • , Marit E. Jørgensen
    • , Anders Albrechtsen
    •  & Torben Hansen
  • Brief Communication |

    Linda Richards, Paul Lockhart, Christel Depienne and colleagues identify heterozygous DCC mutations in four families and five sporadic individuals with agenesis of the corpus callosum (ACC). They report that DCC mutations result in variable dominant phenotypes with incomplete penetrance, including mirror movements and ACC associated with a favorable developmental prognosis.

    • Ashley P L Marsh
    • , Delphine Heron
    • , Timothy J Edwards
    • , Angélique Quartier
    • , Charles Galea
    • , Caroline Nava
    • , Agnès Rastetter
    • , Marie-Laure Moutard
    • , Vicki Anderson
    • , Pierre Bitoun
    • , Jens Bunt
    • , Anne Faudet
    • , Catherine Garel
    • , Greta Gillies
    • , Ilan Gobius
    • , Justine Guegan
    • , Solveig Heide
    • , Boris Keren
    • , Fabien Lesne
    • , Vesna Lukic
    • , Simone A Mandelstam
    • , George McGillivray
    • , Alissandra McIlroy
    • , Aurélie Méneret
    • , Cyril Mignot
    • , Laura R Morcom
    • , Sylvie Odent
    • , Annalisa Paolino
    • , Kate Pope
    • , Florence Riant
    • , Gail A Robinson
    • , Megan Spencer-Smith
    • , Myriam Srour
    • , Sarah E M Stephenson
    • , Rick Tankard
    • , Oriane Trouillard
    • , Quentin Welniarz
    • , Amanda Wood
    • , Alexis Brice
    • , Guy Rouleau
    • , Tania Attié-Bitach
    • , Martin B Delatycki
    • , Jean-Louis Mandel
    • , David J Amor
    • , Emmanuel Roze
    • , Amélie Piton
    • , Melanie Bahlo
    • , Thierry Billette de Villemeur
    • , Elliott H Sherr
    • , Richard J Leventer
    • , Linda J Richards
    • , Paul J Lockhart
    •  & Christel Depienne
  • Brief Communication |

    Timothy Chan and colleagues find that somatic mutations in SERPINB3 or SERPINB4 are associated with longer survival in patients with melanoma who received anti-CTLA4 immunotherapy. These findings may have implications for precision medicine efforts in cancer.

    • Nadeem Riaz
    • , Jonathan J Havel
    • , Sviatoslav M Kendall
    • , Vladimir Makarov
    • , Logan A Walsh
    • , Alexis Desrichard
    • , Nils Weinhold
    •  & Timothy A Chan
  • Brief Communication |

    Johannes Beckers, Martin Hrabě de Angelis and colleagues use in vitro fertilization to demonstrate epigenetic germline inheritance of acquired metabolic disorders in mice. They show that a parental high-fat diet renders offspring more susceptible to developing obesity and diabetes.

    • Peter Huypens
    • , Steffen Sass
    • , Moya Wu
    • , Daniela Dyckhoff
    • , Matthias Tschöp
    • , Fabian Theis
    • , Susan Marschall
    • , Martin Hrabě de Angelis
    •  & Johannes Beckers
  • Brief Communication |

    David Solit and colleagues report that inactivating CDH1 mutations are found in 84% of plasmacytoid bladder cancer samples tested and are not found in other bladder cancer subtypes. CRISPR/Cas9-mediated knockout of CDH1 in cell lines leads to enhanced cellular migration.

    • Hikmat A Al-Ahmadie
    • , Gopa Iyer
    • , Byron H Lee
    • , Sasinya N Scott
    • , Rohit Mehra
    • , Aditya Bagrodia
    • , Emmet J Jordan
    • , Sizhi Paul Gao
    • , Ricardo Ramirez
    • , Eugene K Cha
    • , Neil B Desai
    • , Emily C Zabor
    • , Irina Ostrovnaya
    • , Anuradha Gopalan
    • , Ying-Bei Chen
    • , Samson W Fine
    • , Satish K Tickoo
    • , Anupama Gandhi
    • , Joseph Hreiki
    • , Agnès Viale
    • , Maria E Arcila
    • , Guido Dalbagni
    • , Jonathan E Rosenberg
    • , Bernard H Bochner
    • , Dean F Bajorin
    • , Michael F Berger
    • , Victor E Reuter
    • , Barry S Taylor
    •  & David B Solit
  • Brief Communication |

    Rogier Versteeg and colleagues analyze the whole-genome sequences of 108 neuroblastoma samples and detect structural rearrangements of TERT in 23% of high-stage cases. TERT rearrangements are associated with increased TERT expression, increased telomere length and very poor prognosis.

    • Linda J Valentijn
    • , Jan Koster
    • , Danny A Zwijnenburg
    • , Nancy E Hasselt
    • , Peter van Sluis
    • , Richard Volckmann
    • , Max M van Noesel
    • , Rani E George
    • , Godelieve A M Tytgat
    • , Jan J Molenaar
    •  & Rogier Versteeg
  • Brief Communication |

    Yardena Samuels and colleagues report the analysis of 501 melanoma exomes and the identification of RASA2 as a tumor-suppressor gene mutated in 5% of melanomas. RASA2 mutations led to increased RAS activation, and RASA2 loss was associated with shorter patient survival times.

    • Rand Arafeh
    • , Nouar Qutob
    • , Rafi Emmanuel
    • , Alona Keren-Paz
    • , Jason Madore
    • , Abdel Elkahloun
    • , James S Wilmott
    • , Jared J Gartner
    • , Antonella Di Pizio
    • , Sabina Winograd-Katz
    • , Sivasish Sindiri
    • , Ron Rotkopf
    • , Ken Dutton-Regester
    • , Peter Johansson
    • , Antonia L Pritchard
    • , Nicola Waddell
    • , Victoria K Hill
    • , Jimmy C Lin
    • , Yael Hevroni
    • , Steven A Rosenberg
    • , Javed Khan
    • , Shifra Ben-Dor
    • , Masha Y Niv
    • , Igor Ulitsky
    • , Graham J Mann
    • , Richard A Scolyer
    • , Nicholas K Hayward
    •  & Yardena Samuels
  • Brief Communication |

    Christopher Gordon, Cecilia Lo, Patrice Bouvagnet and colleagues report loss-of-function mutations in the MMP21 gene (encoding matrix metallopeptidase 21) that cause human heterotaxy with associated complex congenital heart defects. The authors confirm the role of MMP21 in heterotaxy and left-right patterning in zebrafish and mouse models.

    • Anne Guimier
    • , George C Gabriel
    • , Fanny Bajolle
    • , Michael Tsang
    • , Hui Liu
    • , Aaron Noll
    • , Molly Schwartz
    • , Rajae El Malti
    • , Laurie D Smith
    • , Nikolai T Klena
    • , Gina Jimenez
    • , Neil A Miller
    • , Myriam Oufadem
    • , Anne Moreau de Bellaing
    • , Hisato Yagi
    • , Carol J Saunders
    • , Candice N Baker
    • , Sylvie Di Filippo
    • , Kevin A Peterson
    • , Isabelle Thiffault
    • , Christine Bole-Feysot
    • , Linda D Cooley
    • , Emily G Farrow
    • , Cécile Masson
    • , Patric Schoen
    • , Jean-François Deleuze
    • , Patrick Nitschké
    • , Stanislas Lyonnet
    • , Loic de Pontual
    • , Stephen A Murray
    • , Damien Bonnet
    • , Stephen F Kingsmore
    • , Jeanne Amiel
    • , Patrice Bouvagnet
    • , Cecilia W Lo
    •  & Christopher T Gordon
  • Brief Communication |

    Hajime Okita and colleagues show that clear-cell sarcoma of the kidney (CCSK) is characterized by recurrent in-frame, internal tandem duplications in BCOR. They detected BCOR alterations in all 20 CCSK tumors analyzed but not in any other pediatric renal tumors, suggesting a specific role for these in-frame duplications in driving CCSK oncogenesis.

    • Hitomi Ueno-Yokohata
    • , Hajime Okita
    • , Keiko Nakasato
    • , Shingo Akimoto
    • , Jun-ichi Hata
    • , Tsugumichi Koshinaga
    • , Masahiro Fukuzawa
    •  & Nobutaka Kiyokawa
  • Brief Communication |

    Jean-Luc Battini, Giovanni Coppola and colleagues identify XPR1 mutations in several families with primary brain calcification. They further show that these mutations alter phosphate export activity, implicating defective phosphate homeostasis in the etiology of this disease.

    • Andrea Legati
    • , Donatella Giovannini
    • , Gaël Nicolas
    • , Uriel López-Sánchez
    • , Beatriz Quintáns
    • , João R M Oliveira
    • , Renee L Sears
    • , Eliana Marisa Ramos
    • , Elizabeth Spiteri
    • , María-Jesús Sobrido
    • , Ángel Carracedo
    • , Cristina Castro-Fernández
    • , Stéphanie Cubizolle
    • , Brent L Fogel
    • , Cyril Goizet
    • , Joanna C Jen
    • , Suppachok Kirdlarp
    • , Anthony E Lang
    • , Zosia Miedzybrodzka
    • , Witoon Mitarnun
    • , Martin Paucar
    • , Henry Paulson
    • , Jérémie Pariente
    • , Anne-Claire Richard
    • , Naomi S Salins
    • , Sheila A Simpson
    • , Pasquale Striano
    • , Per Svenningsson
    • , François Tison
    • , Vivek K Unni
    • , Olivier Vanakker
    • , Marja W Wessels
    • , Suppachok Wetchaphanphesat
    • , Michele Yang
    • , Francois Boller
    • , Dominique Campion
    • , Didier Hannequin
    • , Marc Sitbon
    • , Daniel H Geschwind
    • , Jean-Luc Battini
    •  & Giovanni Coppola
  • Brief Communication |

    Cisca Wijmenga and colleagues report fine mapping of the association signal in the MHC region in individuals with celiac disease. They identify five additional risk factors that are independent of HLA-DQ alleles and that account for 18% of the genetic risk for this disease.

    • Javier Gutierrez-Achury
    • , Alexandra Zhernakova
    • , Sara L Pulit
    • , Gosia Trynka
    • , Karen A Hunt
    • , Jihane Romanos
    • , Soumya Raychaudhuri
    • , David A van Heel
    • , Cisca Wijmenga
    •  & Paul I W de Bakker
  • Brief Communication |

    Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States.

    • Stacy Steinberg
    • , Hreinn Stefansson
    • , Thorlakur Jonsson
    • , Hrefna Johannsdottir
    • , Andres Ingason
    • , Hannes Helgason
    • , Patrick Sulem
    • , Olafur Th Magnusson
    • , Sigurjon A Gudjonsson
    • , Unnur Unnsteinsdottir
    • , Augustine Kong
    • , Seppo Helisalmi
    • , Hilkka Soininen
    • , James J Lah
    • , DemGene
    • , Ina Selseth Almdahl
    • , Fred Andersen
    • , Nenad Bogdanovic
    • , Anne Brækhus
    • , Knut Engedal
    • , Arvid Rongve
    • , Ingvild Saltvedt
    • , Eystein Stordal
    • , Aree Witoelar
    • , Dag Aarsland
    • , Tormod Fladby
    • , Ingun D Ulstein
    • , Srdjan Djurovic
    • , Sigrid B Sando
    • , Linda R White
    • , Gun-Peggy Knudsen
    • , Lars T Westlye
    • , Geir Selbæk
    • , Ina Giegling
    • , Harald Hampel
    • , Mikko Hiltunen
    • , Allan I Levey
    • , Ole A Andreassen
    • , Dan Rujescu
    • , Palmi V Jonsson
    • , Sigurbjorn Bjornsson
    • , Jon Snaedal
    •  & Kari Stefansson
  • Brief Communication |

    Levi Garraway and colleagues report the identification of somatic mutations of RNF43, which encodes an E3 ubiquitin ligase that negatively regulates Wnt signaling, in over 18% of colorectal adenocarcinomas and endometrial carcinomas.

    • Marios Giannakis
    • , Eran Hodis
    • , Xinmeng Jasmine Mu
    • , Mai Yamauchi
    • , Joseph Rosenbluh
    • , Kristian Cibulskis
    • , Gordon Saksena
    • , Michael S Lawrence
    • , Zhi Rong Qian
    • , Reiko Nishihara
    • , Eliezer M Van Allen
    • , William C Hahn
    • , Stacey B Gabriel
    • , Eric S Lander
    • , Gad Getz
    • , Shuji Ogino
    • , Charles S Fuchs
    •  & Levi A Garraway
  • Brief Communication |

    Chetan Bettegowda, Bert Vogelstein and colleagues identify somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors from individuals with and without neurofibromatosis. SUZ12 encodes a chromatin-modifying protein and is located adjacent to the NF1 gene on chromosome 17q11. The data support a 'three-hit' model of tumor suppression.

    • Ming Zhang
    • , Yuxuan Wang
    • , Sian Jones
    • , Mark Sausen
    • , Kevin McMahon
    • , Rajni Sharma
    • , Qing Wang
    • , Allan J Belzberg
    • , Kaisorn Chaichana
    • , Gary L Gallia
    • , Ziya L Gokaslan
    • , Greg J Riggins
    • , Jean-Paul Wolinksy
    • , Laura D Wood
    • , Elizabeth A Montgomery
    • , Ralph H Hruban
    • , Kenneth W Kinzler
    • , Nickolas Papadopoulos
    • , Bert Vogelstein
    •  & Chetan Bettegowda
  • Brief Communication |

    Jorge Reis-Filho and colleagues identify recurrent mutations in PRKD1 in 73% of polymorphous low-grade adenocarcinoma, a malignant tumor of the minor salivary glands. The mutations cause activation of the PRKD1 serine-threonine kinase.

    • Ilan Weinreb
    • , Salvatore Piscuoglio
    • , Luciano G Martelotto
    • , Daryl Waggott
    • , Charlotte K Y Ng
    • , Bayardo Perez-Ordonez
    • , Nicholas J Harding
    • , Javier Alfaro
    • , Kenneth C Chu
    • , Agnes Viale
    • , Nicola Fusco
    • , Arnaud da Cruz Paula
    • , Caterina Marchio
    • , Rita A Sakr
    • , Raymond Lim
    • , Lester D R Thompson
    • , Simion I Chiosea
    • , Raja R Seethala
    • , Alena Skalova
    • , Edward B Stelow
    • , Isabel Fonseca
    • , Adel Assaad
    • , Christine How
    • , Jianxin Wang
    • , Richard de Borja
    • , Michelle Chan-Seng-Yue
    • , Christopher J Howlett
    • , Anthony C Nichols
    • , Y Hannah Wen
    • , Nora Katabi
    • , Nicholas Buchner
    • , Laura Mullen
    • , Thomas Kislinger
    • , Bradly G Wouters
    • , Fei-Fei Liu
    • , Larry Norton
    • , John D McPherson
    • , Brian P Rubin
    • , Blaise A Clarke
    • , Britta Weigelt
    • , Paul C Boutros
    •  & Jorge S Reis-Filho
  • Brief Communication |

    Paul Khavari and colleagues identify recurrent mutations concentrated at an ultraviolet signature hotspot in the KNSTRN gene in 19% of cutaneous squamous cell carcinomas. KNSTRN encodes a kinetochore protein.

    • Carolyn S Lee
    • , Aparna Bhaduri
    • , Angela Mah
    • , Whitney L Johnson
    • , Alexander Ungewickell
    • , Cody J Aros
    • , Christie B Nguyen
    • , Eon J Rios
    • , Zurab Siprashvili
    • , Aaron Straight
    • , Jinah Kim
    • , Sumaira Z Aasi
    •  & Paul A Khavari
  • Brief Communication |

    Andrew Hattersley, Noel Morgan, Juha Kere and colleagues identify de novo activating germline STAT3 mutations in five unrelated individuals with early-onset multi-organ autoimmune disease.

    • Sarah E Flanagan
    • , Emma Haapaniemi
    • , Mark A Russell
    • , Richard Caswell
    • , Hana Lango Allen
    • , Elisa De Franco
    • , Timothy J McDonald
    • , Hanna Rajala
    • , Anita Ramelius
    • , John Barton
    • , Kaarina Heiskanen
    • , Tarja Heiskanen-Kosma
    • , Merja Kajosaari
    • , Nuala P Murphy
    • , Tatjana Milenkovic
    • , Mikko Seppänen
    • , Åke Lernmark
    • , Satu Mustjoki
    • , Timo Otonkoski
    • , Juha Kere
    • , Noel G Morgan
    • , Sian Ellard
    •  & Andrew T Hattersley
  • Brief Communication |

    Marco Tartaglia, Raoul Hennekam and colleagues show that de novo mutations in ZBTB20 cause Primrose syndrome, a disorder characterized by tall stature, macrocephaly, intellectual disability, diabetes, deafness, progressive muscle wasting and ectopic calcifications.

    • Viviana Cordeddu
    • , Bert Redeker
    • , Emilia Stellacci
    • , Aldo Jongejan
    • , Alessandra Fragale
    • , Ted E J Bradley
    • , Massimiliano Anselmi
    • , Andrea Ciolfi
    • , Serena Cecchetti
    • , Valentina Muto
    • , Laura Bernardini
    • , Meron Azage
    • , Daniel R Carvalho
    • , Alberto J Espay
    • , Alison Male
    • , Anna-Maja Molin
    • , Renata Posmyk
    • , Carla Battisti
    • , Alberto Casertano
    • , Daniela Melis
    • , Antoine van Kampen
    • , Frank Baas
    • , Marcel M Mannens
    • , Gianfranco Bocchinfuso
    • , Lorenzo Stella
    • , Marco Tartaglia
    •  & Raoul C Hennekam
  • Brief Communication |

    André Oliveira and colleagues identify a recurrent translocation in biphenotypic sinonasal sarcomas generating a PAX3-MAML3 fusion gene. The resulting protein is a potent transcriptional activator of PAX3 response elements and is associated with aberrant expression of genes involved in neuroectodermal and myogenic differentiation.

    • Xiaoke Wang
    • , Krista L Bledsoe
    • , Rondell P Graham
    • , Yan W Asmann
    • , David S Viswanatha
    • , Jean E Lewis
    • , Jason T Lewis
    • , Margaret M Chou
    • , Michael J Yaszemski
    • , Jin Jen
    • , Jennifer J Westendorf
    •  & André M Oliveira
  • Brief Communication |

    Douglas Levine and colleagues identify recurrent inactivating mutations in the SWI/SNF complex member SMARCA4 in 12 of 12 samples of small cell carcinoma of the ovary, hypercalcemic type. These findings open the door for the development of targeted therapies to treat this rare but deadly cancer.

    • Petar Jelinic
    • , Jennifer J Mueller
    • , Narciso Olvera
    • , Fanny Dao
    • , Sasinya N Scott
    • , Ronak Shah
    • , JianJiong Gao
    • , Nikolaus Schultz
    • , Mithat Gonen
    • , Robert A Soslow
    • , Michael F Berger
    •  & Douglas A Levine
  • Brief Communication |

    Jeffrey Trent, David Huntsman and colleagues identify the SWI/SNF chromatin-remodeling gene SMARCA4 as commonly mutated in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Their results implicate SMARCA4 as a crucial factor in the oncogenesis of SCCOHT, a rare but highly malignant cancer.

    • Pilar Ramos
    • , Anthony N Karnezis
    • , David W Craig
    • , Aleksandar Sekulic
    • , Megan L Russell
    • , William P D Hendricks
    • , Jason J Corneveaux
    • , Michael T Barrett
    • , Karey Shumansky
    • , Yidong Yang
    • , Sohrab P Shah
    • , Leah M Prentice
    • , Marco A Marra
    • , Jeffrey Kiefer
    • , Victoria L Zismann
    • , Troy A McEachron
    • , Bodour Salhia
    • , Jaime Prat
    • , Emanuela D'Angelo
    • , Blaise A Clarke
    • , Joseph G Pressey
    • , John H Farley
    • , Stephen P Anthony
    • , Richard B S Roden
    • , Heather E Cunliffe
    • , David G Huntsman
    •  & Jeffrey M Trent
  • Brief Communication |

    Richard Thompson, Melissa Sambrotta and colleagues show that biallelic mutations in TJP2 cause severe cholestatic liver disease. Their findings suggest that loss of TJP2 protein disrupts the structural integrity of tight junctions in liver tissue, resulting in progressive liver damage.

    • Melissa Sambrotta
    • , Sandra Strautnieks
    • , Efterpi Papouli
    • , Peter Rushton
    • , Barnaby E Clark
    • , David A Parry
    • , Clare V Logan
    • , Lucy J Newbury
    • , Binita M Kamath
    • , Simon Ling
    • , Tassos Grammatikopoulos
    • , Bart E Wagner
    • , John C Magee
    • , Ronald J Sokol
    • , Giorgina Mieli-Vergani
    • , University of Washington Center for Mendelian Genomics
    • , Joshua D Smith
    • , Colin A Johnson
    • , Patricia McClean
    • , Michael A Simpson
    • , A S Knisely
    • , Laura N Bull
    •  & Richard J Thompson
  • Brief Communication |

    Paul Meltzer and colleagues report the results of an exome sequencing study of variant and IGHV4-34–expressing hairy-cell leukemias. They identify a high frequency of activating MAP2K1 mutations in these malignancies, suggesting potential therapeutic strategies.

    • Joshua J Waterfall
    • , Evgeny Arons
    • , Robert L Walker
    • , Marbin Pineda
    • , Laura Roth
    • , J Keith Killian
    • , Ogan D Abaan
    • , Sean R Davis
    • , Robert J Kreitman
    •  & Paul S Meltzer
  • Brief Communication |

    Todd Waldman and colleagues screened 2,214 tumors for loss of STAG2 expression using immunohistochemistry. They followed up by sequencing STAG2 in 111 urothelial carcinomas and found mutations in 23 of the cases, identifying STAG2 as one of the most commonly mutated genes in bladder cancer.

    • David A Solomon
    • , Jung-Sik Kim
    • , Jolanta Bondaruk
    • , Shahrokh F Shariat
    • , Zeng-Feng Wang
    • , Abdel G Elkahloun
    • , Tomoko Ozawa
    • , Julia Gerard
    • , DaZhong Zhuang
    • , Shizhen Zhang
    • , Neema Navai
    • , Arlene Siefker-Radtke
    • , Joanna J Phillips
    • , Brian D Robinson
    • , Mark A Rubin
    • , Björn Volkmer
    • , Richard Hautmann
    • , Rainer Küfer
    • , Pancras C W Hogendoorn
    • , George Netto
    • , Dan Theodorescu
    • , C David James
    • , Bogdan Czerniak
    • , Markku Miettinen
    •  & Todd Waldman
  • Brief Communication |

    William Harbour, Anne Bowcock and colleagues identify recurrent mutations at codon 625 of SF3B1 in uveal melanomas. These mutations occur in low-grade tumors and are associated with favorable prognosis.

    • J William Harbour
    • , Elisha D O Roberson
    • , Hima Anbunathan
    • , Michael D Onken
    • , Lori A Worley
    •  & Anne M Bowcock
  • Brief Communication |

    Matthew Meyerson and colleagues report exome sequencing of solitary fibrous tumor (SFT), a rare mesenchymal tumor. They identify a NAB2-STAT6 fusion in 55% of cases.

    • Juliann Chmielecki
    • , Aimee M Crago
    • , Mara Rosenberg
    • , Rachael O'Connor
    • , Sarah R Walker
    • , Lauren Ambrogio
    • , Daniel Auclair
    • , Aaron McKenna
    • , Michael C Heinrich
    • , David A Frank
    •  & Matthew Meyerson
  • Brief Communication |

    Samuel Berkovic and colleagues report the identification of missense mutations in KCNT1, which encodes a sodium-gated potassium channel, that cause severe autosomal dominant nocturnal frontal lobe epilepsy.

    • Sarah E Heron
    • , Katherine R Smith
    • , Melanie Bahlo
    • , Lino Nobili
    • , Esther Kahana
    • , Laura Licchetta
    • , Karen L Oliver
    • , Aziz Mazarib
    • , Zaid Afawi
    • , Amos Korczyn
    • , Giuseppe Plazzi
    • , Steven Petrou
    • , Samuel F Berkovic
    • , Ingrid E Scheffer
    •  & Leanne M Dibbens
  • Brief Communication |

    Adrienne Flanagan and colleagues identify a common variant in the T gene associated with strong risk of chordoma, a rare malignant bone tumor. The risk variant alters an amino acid in the DNA-binding domain of the T transcription factor and is associated with differential expression of T and its downstream targets.

    • Nischalan Pillay
    • , Vincent Plagnol
    • , Patrick S Tarpey
    • , Samira B Lobo
    • , Nadège Presneau
    • , Karoly Szuhai
    • , Dina Halai
    • , Fitim Berisha
    • , Stephen R Cannon
    • , Simon Mead
    • , Dalia Kasperaviciute
    • , Jutta Palmen
    • , Philippa J Talmud
    • , Lars-Gunnar Kindblom
    • , M Fernanda Amary
    • , Roberto Tirabosco
    •  & Adrienne M Flanagan
  • Brief Communication |

    Ross Levine, Lambert Busque and colleagues report the identification of recurrent somatic mutations in TET2 in elderly female individuals with clonal hematopoiesis. The mutations were identified in individuals without clinically apparent hematological malignancies.

    • Lambert Busque
    • , Jay P Patel
    • , Maria E Figueroa
    • , Aparna Vasanthakumar
    • , Sylvie Provost
    • , Zineb Hamilou
    • , Luigina Mollica
    • , Juan Li
    • , Agnes Viale
    • , Adriana Heguy
    • , Maryam Hassimi
    • , Nicholas Socci
    • , Parva K Bhatt
    • , Mithat Gonen
    • , Christopher E Mason
    • , Ari Melnick
    • , Lucy A Godley
    • , Cameron W Brennan
    • , Omar Abdel-Wahab
    •  & Ross L Levine
  • Brief Communication |

    Nick Orr and colleagues report a genome-wide association study for male breast cancer. They identify a new susceptibility locus at RAD51B and examine association evidence for known female breast cancer loci in these cohorts.

    • Nick Orr
    • , Alina Lemnrau
    • , Rosie Cooke
    • , Olivia Fletcher
    • , Katarzyna Tomczyk
    • , Michael Jones
    • , Nichola Johnson
    • , Christopher J Lord
    • , Costas Mitsopoulos
    • , Marketa Zvelebil
    • , Simon S McDade
    • , Gemma Buck
    • , Christine Blancher
    • , KConFab Consortium
    • , Alison H Trainer
    • , Paul A James
    • , Stig E Bojesen
    • , Susanne Bokmand
    • , Heli Nevanlinna
    • , Johanna Mattson
    • , Eitan Friedman
    • , Yael Laitman
    • , Domenico Palli
    • , Giovanna Masala
    • , Ines Zanna
    • , Laura Ottini
    • , Giuseppe Giannini
    • , Antoinette Hollestelle
    • , Ans M W van den Ouweland
    • , Srdjan Novaković
    • , Mateja Krajc
    • , Manuela Gago-Dominguez
    • , Jose Esteban Castelao
    • , Håkan Olsson
    • , Ingrid Hedenfalk
    • , Douglas F Easton
    • , Paul D P Pharoah
    • , Alison M Dunning
    • , D Timothy Bishop
    • , Susan L Neuhausen
    • , Linda Steele
    • , Richard S Houlston
    • , Montserrat Garcia-Closas
    • , Alan Ashworth
    •  & Anthony J Swerdlow
  • Brief Communication |

    Albena Jordanova and colleagues report mutations in HINT1 in autosomal recessive axonal neuropathy with neuromyotonia. Using linkage analysis and whole-genome sequencing, they identify 8 mutations in 33 affected families.

    • Magdalena Zimoń
    • , Jonathan Baets
    • , Leonardo Almeida-Souza
    • , Els De Vriendt
    • , Jelena Nikodinovic
    • , Yesim Parman
    • , Esra Battaloǧlu
    • , Zeliha Matur
    • , Velina Guergueltcheva
    • , Ivailo Tournev
    • , Michaela Auer-Grumbach
    • , Peter De Rijk
    • , Britt-Sabina Petersen
    • , Thomas Müller
    • , Erik Fransen
    • , Philip Van Damme
    • , Wolfgang N Löscher
    • , Nina Barišić
    • , Zoran Mitrovic
    • , Stefano C Previtali
    • , Haluk Topaloǧlu
    • , Günther Bernert
    • , Ana Beleza-Meireles
    • , Slobodanka Todorovic
    • , Dusanka Savic-Pavicevic
    • , Boryana Ishpekova
    • , Silvia Lechner
    • , Kristien Peeters
    • , Tinne Ooms
    • , Angelika F Hahn
    • , Stephan Züchner
    • , Vincent Timmerman
    • , Patrick Van Dijck
    • , Vedrana Milic Rasic
    • , Andreas R Janecke
    • , Peter De Jonghe
    •  & Albena Jordanova
  • Brief Communication |

    Alex Meissner and colleagues report base pair–resolution methylation maps from donor fibroblasts and nuclear transfer–reconstructed mouse embryos. They compare methylation profiles to that present during normal fertilization and find that specific promoters and repeat elements exhibit differential dynamics.

    • Michelle M Chan
    • , Zachary D Smith
    • , Dieter Egli
    • , Aviv Regev
    •  & Alexander Meissner
  • Brief Communication |

    Elisabeth Mangold and colleagues report a genome-wide meta-analyses of non-syndromic cleft lip with or without cleft palate (NSCL/P). They report six new genetic loci associated with risk for NSCL/P.

    • Kerstin U Ludwig
    • , Elisabeth Mangold
    • , Stefan Herms
    • , Stefanie Nowak
    • , Heiko Reutter
    • , Anna Paul
    • , Jessica Becker
    • , Ruth Herberz
    • , Taofik AlChawa
    • , Entessar Nasser
    • , Anne C Böhmer
    • , Manuel Mattheisen
    • , Margrieta A Alblas
    • , Sandra Barth
    • , Nadine Kluck
    • , Carola Lauster
    • , Bert Braumann
    • , Rudolf H Reich
    • , Alexander Hemprich
    • , Simone Pötzsch
    • , Bettina Blaumeiser
    • , Nikolaos Daratsianos
    • , Thomas Kreusch
    • , Jeffrey C Murray
    • , Mary L Marazita
    • , Ingo Ruczinski
    • , Alan F Scott
    • , Terri H Beaty
    • , Franz-Josef Kramer
    • , Thomas F Wienker
    • , Regine P Steegers-Theunissen
    • , Michele Rubini
    • , Peter A Mossey
    • , Per Hoffmann
    • , Christoph Lange
    • , Sven Cichon
    • , Peter Propping
    • , Michael Knapp
    •  & Markus M Nöthen
  • Brief Communication |

    Josseline Kaplan, Jean-Michel Rozet and colleagues show that biallelic mutations in NMNAT1 cause an autosomal recessive form of Leber congenital amaurosis characterized by early-onset severe macular atrophy and optic atrophy.

    • Isabelle Perrault
    • , Sylvain Hanein
    • , Xavier Zanlonghi
    • , Valérie Serre
    • , Michael Nicouleau
    • , Sabine Defoort-Delhemmes
    • , Nathalie Delphin
    • , Lucas Fares-Taie
    • , Sylvie Gerber
    • , Olivia Xerri
    • , Catherine Edelson
    • , Alice Goldenberg
    • , Alice Duncombe
    • , Gylène Le Meur
    • , Christian Hamel
    • , Eduardo Silva
    • , Patrick Nitschke
    • , Patrick Calvas
    • , Arnold Munnich
    • , Olivier Roche
    • , Hélène Dollfus
    • , Josseline Kaplan
    •  & Jean-Michel Rozet
  • Brief Communication |

    Ming Qi and colleagues report that compound heterozygous mutations in NMNAT1 cause Leber congenital amaurosis, a childhood form of retinal dystrophy. NMNAT1 encodes an enzyme previously implicated in protection against axonal degeneration.

    • Pei-Wen Chiang
    • , Juan Wang
    • , Yang Chen
    • , Quan Fu
    • , Jing Zhong
    • , Yanhua Chen
    • , Xin Yi
    • , Renhua Wu
    • , Haixue Gan
    • , Yong Shi
    • , Yanling Chen
    • , Christopher Barnett
    • , Dianna Wheaton
    • , Megan Day
    • , Joanne Sutherland
    • , Elise Heon
    • , Richard G Weleber
    • , Luis Alexandre Rassi Gabriel
    • , Peikuan Cong
    • , KuangHsiang Chuang
    • , Sheng Ye
    • , Juliana Maria Ferraz Sallum
    •  & Ming Qi
  • Brief Communication |

    Adrian Clark and colleagues report mutations in the NNT gene encoding nicotinamide nucleotide transhydrogenase in familial glucocorticoid deficiency (FGD).

    • Eirini Meimaridou
    • , Julia Kowalczyk
    • , Leonardo Guasti
    • , Claire R Hughes
    • , Florian Wagner
    • , Peter Frommolt
    • , Peter Nürnberg
    • , Nicholas P Mann
    • , Ritwik Banerjee
    • , H Nurcin Saka
    • , J Paul Chapple
    • , Peter J King
    • , Adrian J L Clark
    •  & Louise A Metherell
  • Brief Communication |

    Marcella Zollino and colleagues report mutations in the chromatin regulator KANSL1 in persons with 17q21.31 syndrome. This disorder is marked by distinctive facial features, moderate-to-severe intellectual disability, hypotonia and friendly behavior.

    • Marcella Zollino
    • , Daniela Orteschi
    • , Marina Murdolo
    • , Serena Lattante
    • , Domenica Battaglia
    • , Chiara Stefanini
    • , Eugenio Mercuri
    • , Pietro Chiurazzi
    • , Giovanni Neri
    •  & Giuseppe Marangi
  • Brief Communication |

    Bert DeVries and colleagues identify mutations in the chromatin regulator KANSL1 in 17q21.31 microdeletion syndrome. This syndrome is characterized by intellectual disability, hypotonia and distinctive facial features.

    • David A Koolen
    • , Jamie M Kramer
    • , Kornelia Neveling
    • , Willy M Nillesen
    • , Heather L Moore-Barton
    • , Frances V Elmslie
    • , Annick Toutain
    • , Jeanne Amiel
    • , Valérie Malan
    • , Anne Chun-Hui Tsai
    • , Sau Wai Cheung
    • , Christian Gilissen
    • , Eugene T P Verwiel
    • , Sarah Martens
    • , Ton Feuth
    • , Ernie M H F Bongers
    • , Petra de Vries
    • , Hans Scheffer
    • , Lisenka E L M Vissers
    • , Arjan P M de Brouwer
    • , Han G Brunner
    • , Joris A Veltman
    • , Annette Schenck
    • , Helger G Yntema
    •  & Bert B A de Vries
  • Brief Communication |

    Gijs Santen and colleagues report mutations in the SWI/SNF subunit gene ARID1B in Coffin-Siris syndrome.

    • Gijs W E Santen
    • , Emmelien Aten
    • , Yu Sun
    • , Rowida Almomani
    • , Christian Gilissen
    • , Maartje Nielsen
    • , Sarina G Kant
    • , Irina N Snoeck
    • , Els A J Peeters
    • , Yvonne Hilhorst-Hofstee
    • , Marja W Wessels
    • , Nicolette S den Hollander
    • , Claudia A L Ruivenkamp
    • , Gert-Jan B van Ommen
    • , Martijn H Breuning
    • , Johan T den Dunnen
    • , Arie van Haeringen
    •  & Marjolein Kriek
  • Brief Communication |

    Naomichi Matsumoto and colleagues report mutations in the SWI/SNF chromatin remodeling complex in Coffin-Siris syndrome. Twenty affected individuals (87%) harbored mutations in one of six SWI/SNF subunit genes: SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A or ARID1B.

    • Yoshinori Tsurusaki
    • , Nobuhiko Okamoto
    • , Hirofumi Ohashi
    • , Tomoki Kosho
    • , Yoko Imai
    • , Yumiko Hibi-Ko
    • , Tadashi Kaname
    • , Kenji Naritomi
    • , Hiroshi Kawame
    • , Keiko Wakui
    • , Yoshimitsu Fukushima
    • , Tomomi Homma
    • , Mitsuhiro Kato
    • , Yoko Hiraki
    • , Takanori Yamagata
    • , Shoji Yano
    • , Seiji Mizuno
    • , Satoru Sakazume
    • , Takuma Ishii
    • , Toshiro Nagai
    • , Masaaki Shiina
    • , Kazuhiro Ogata
    • , Tohru Ohta
    • , Norio Niikawa
    • , Satoko Miyatake
    • , Ippei Okada
    • , Takeshi Mizuguchi
    • , Hiroshi Doi
    • , Hirotomo Saitsu
    • , Noriko Miyake
    •  & Naomichi Matsumoto
  • Brief Communication |

    Xue Zhang, Jing Yu Liu and colleagues report SLC20A2 mutations in familial idiopathic basal ganglia calcification (IBGC, also known as Fahr disease). These mutations impair the function of the type III phosphate transporter encoded by SLA20A2 and may disturb phosphate homeostasis in the body.

    • Cheng Wang
    • , Yulei Li
    • , Lei Shi
    • , Jie Ren
    • , Monica Patti
    • , Tao Wang
    • , João R M de Oliveira
    • , María-Jesús Sobrido
    • , Beatriz Quintáns
    • , Miguel Baquero
    • , Xiaoniu Cui
    • , Xiang-Yang Zhang
    • , Lianqing Wang
    • , Haibo Xu
    • , Junhan Wang
    • , Jing Yao
    • , Xiaohua Dai
    • , Juan Liu
    • , Lu Zhang
    • , Hongying Ma
    • , Yong Gao
    • , Xixiang Ma
    • , Shenglei Feng
    • , Mugen Liu
    • , Qing K Wang
    • , Ian C Forster
    • , Xue Zhang
    •  & Jing-Yu Liu
  • Brief Communication |

    Christian Meyer and colleagues follow a previously reported GWAS for tuberculosis susceptibility with association analyses using 1000 Genomes Project imputation in two African studies and replication in Indonesian and Russian cohorts. They identify a new tuberculosis susceptibility locus on chromosome 11p13.

    • Thorsten Thye
    • , Ellis Owusu-Dabo
    • , Fredrik O Vannberg
    • , Reinout van Crevel
    • , James Curtis
    • , Edhyana Sahiratmadja
    • , Yanina Balabanova
    • , Christa Ehmen
    • , Birgit Muntau
    • , Gerd Ruge
    • , Jürgen Sievertsen
    • , John Gyapong
    • , Vladyslav Nikolayevskyy
    • , Philip C Hill
    • , Giorgio Sirugo
    • , Francis Drobniewski
    • , Esther van de Vosse
    • , Melanie Newport
    • , Bachti Alisjahbana
    • , Sergey Nejentsev
    • , Tom H M Ottenhoff
    • , Adrian V S Hill
    • , Rolf D Horstmann
    •  & Christian G Meyer
  • Brief Communication |

    Suzanne Baker and colleagues sequenced the whole genomes of seven pediatric brainstem glioblastomas and matched normal tissue. They found that 78% of diffuse intrinsic pontine gliomas and 22% of non-brainstem pediatric glioblastomas contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, causing a p.Lys27Met amino acid substitution in each protein.

    • St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
    • , Gang Wu
    • , Alberto Broniscer
    • , Troy A McEachron
    • , Charles Lu
    • , Barbara S Paugh
    • , Jared Becksfort
    • , Chunxu Qu
    • , Li Ding
    • , Robert Huether
    • , Matthew Parker
    • , Junyuan Zhang
    • , Amar Gajjar
    • , Michael A Dyer
    • , Charles G Mullighan
    • , Richard J Gilbertson
    • , Elaine R Mardis
    • , Richard K Wilson
    • , James R Downing
    • , David W Ellison
    • , Jinghui Zhang
    •  & Suzanne J Baker
  • Brief Communication |

    Andrew Hattersley and colleagues report an exome sequencing study that identifies de novo heterozygous inactivating mutations in GATA6 as a common cause of pancreatic agenesis. This suggests an essential function for GATA6 in human pancreas development.

    • Hana Lango Allen
    • , Sarah E Flanagan
    • , Charles Shaw-Smith
    • , Elisa De Franco
    • , Ildem Akerman
    • , Richard Caswell
    • , the International Pancreatic Agenesis Consortium
    • , Jorge Ferrer
    • , Andrew T Hattersley
    •  & Sian Ellard
  • Brief Communication |

    Huanming Yang, Zhiming Cai, Jun Wang and colleagues report whole-exome sequencing of 10 clear cell renal cell carcinomas followed by a screen of ~1,100 genes in a total of 98 tumors. They found 12 new disease-associated genes and detected frequent alterations in the ubiquitin-mediated proteolysis pathway.

    • Guangwu Guo
    • , Yaoting Gui
    • , Shengjie Gao
    • , Aifa Tang
    • , Xueda Hu
    • , Yi Huang
    • , Wenlong Jia
    • , Zesong Li
    • , Minghui He
    • , Liang Sun
    • , Pengfei Song
    • , Xiaojuan Sun
    • , Xiaokun Zhao
    • , Sangming Yang
    • , Chaozhao Liang
    • , Shengqing Wan
    • , Fangjian Zhou
    • , Chao Chen
    • , Jialou Zhu
    • , Xianxin Li
    • , Minghan Jian
    • , Liang Zhou
    • , Rui Ye
    • , Peide Huang
    • , Jing Chen
    • , Tao Jiang
    • , Xiao Liu
    • , Yong Wang
    • , Jing Zou
    • , Zhimao Jiang
    • , Renhua Wu
    • , Song Wu
    • , Fan Fan
    • , Zhongfu Zhang
    • , Lin Liu
    • , Ruilin Yang
    • , Xingwang Liu
    • , Haibo Wu
    • , Weihua Yin
    • , Xia Zhao
    • , Yuchen Liu
    • , Huanhuan Peng
    • , Binghua Jiang
    • , Qingxin Feng
    • , Cailing Li
    • , Jun Xie
    • , Jingxiao Lu
    • , Karsten Kristiansen
    • , Yingrui Li
    • , Xiuqing Zhang
    • , Songgang Li
    • , Jian Wang
    • , Huanming Yang
    • , Zhiming Cai
    •  & Jun Wang