Biallelic pathogenic variants in PIBF1 have been identified as one of the genetic etiologies of Joubert syndrome. We report a two-year-old girl with global developmental delay, facial dysmorphism, hypotonia, enlarged cystic kidneys, molar tooth sign, and thinning of corpus callosum. A novel homozygous 36-bp insertion in PIBF1 (c.1181_1182ins36) was identified by exome sequencing as the likely cause of her condition. This is the second publication demonstrating the cause and effect relationship between PIBF1 and Joubert syndrome.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Kim K, Lee K, Rhee K. CEP90 is required for the assembly and centrosomal accumulation of centriolar satellites, which is essential for primary cilia formation. PLoS ONE. 2012;7:e48196.
Wheway G, Schmidts M, Mans DA, Szymanska K, Nguyen TM, Racher H, et al. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nat Cell Biol. 2015;17:1074–87.
Guo Y, Ding X, Shen Y, Lyon GJ, Wang K. SeqMule: automated pipeline for analysis of human exome/genome sequencing data. Sci Rep. 2015;5:14283.
Shukla A, Hebbar M, Srivastava A, Kadavigere R, Upadhyai P, Kanthi A, et al. Homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome. J Hum Genet. 2017;62:723–7.
van Dam TJ, Wheway G, Slaats GG, Huynen MA, Giles RH. The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium. Cilia. 2013;2:7.
Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14:178–92.
Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.
Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 2009;37:e67.
Choi Y, Chan AP. PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics. 2015;31:2745–7.
Limongelli I, Marini S, Bellazzi R. PaPI: pseudo amino acid composition to score human protein-coding variants. BMC Bioinform. 2015;16:123.
Hu J, Ng PC. SIFT Indel: predictions for the functional effects of amino acid insertions/deletions in proteins. PLoS ONE. 2013;8:e77940.
We thank the family who cooperated with evaluation of the children and consented for participation in this study.
This work was supported by National Institutes of Health funded the project titled “Genetic Diagnosis of Heritable Neurodevelopmental Disorders in India: Investigating the Use of Whole Exome Sequencing and Genetic Counseling to Address the High Burden of Neurodevelopmental Disorders”(1R21NS094047-01).
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
About this article
Cite this article
Hebbar, M., Kanthi, A., Shukla, A. et al. A biallelic 36-bp insertion in PIBF1 is associated with Joubert syndrome. J Hum Genet 63, 935–939 (2018). https://doi.org/10.1038/s10038-018-0462-7