Nature Genetics
16, 54 - 63 (1997)
doi:10.1038/ng0597-54
Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndromeErcole Rao1, Birgit Weiss1, Maki Fukami1, 2, *, Andreas Rump3, *, Beate Niesler1, Annelyse Mertz1, Koji Muroya2, Gerhard Binder4, Stefan Kirsch1, Martina Winkelmann1, Gabriele Nordsiek3, Udo Heinrich5, Martijn H. Breuning6, 7, Michael B. Ranke4, André Rosenthal3, Tsutomu Ogata2
& Gudrun A. Rappold1, 8
1Institute of Human Genetics, Heidelberg University, Im Neuenheimer Feld 328,69120 Heidelberg, Germany.
2Department of Paediatrics, Keio University, 35 Shinanomachi Shinjuku, Tokyo 160, Japan.
3Institute of Molecular Biotechnology, Department of Genome Analysis, Beutenbergstrafiell, 07745 Jena, Germany.
4Section ofPaediatric Endocrinology at the Children's Hospital, Tubingen University, Ruemelinstr. 23,72070 Tubingen, Germany.
5Department of Paediatrics at the Children's Hospital, Heidelberg University, Im Neuenheimer Feld 150,69120 Heidelberg, Germany.
6Department of Human Genetics, Leiden University, SylviusLab, Wassenaarse-weg72,2300 RA Leiden, The Netherlands.
7Department of Clinical Genetics, Dijkzigt Hospital, Erasmus University, Rotterdam, The Netherlands. M.R & A.R. contributed equally to this work.
8e-mail: gudrun_rappold@krzmail.krz.uni-heidelberg.de Growth retardation resulting in short stature is a major concern for parents and due to its great variety of causes, a complex diagnostic challenge for clinicians. A major locus involved in linear growth has been implicated within the pseudoautosomal region (PAR1) of the human sex chromosomes. We have determined an interval of 170 kb of DNA within PAR1 which was deleted in 36 individuals with short stature and different rearrangements on Xp22 or Yp11.3. This deletion was not detected in any of the relatives with normal stature or in a further 30 individuals with rearrangements on Xp22 or Yp11.3 with normal height. We have isolated a homeobox-containing gene (SHOX} from this region, which has at least two alternatively spliced forms, encoding proteins with different patterns of expression. We also identified one functionally significant SHOX mutation by screening 91 individuals with idiopathic short stature. Our data suggest an involvement of SHOX in idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients.
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