Journal article
Pathogenic Variants in GPC4 Cause Keipert Syndrome
DJ Amor, SEM Stephenson, M Mustapha, MA Mensah, CW Ockeloen, WS Lee, RM Tankard, DG Phelan, M Shinawi, APM de Brouwer, R Pfundt, C Dowling, TL Toler, VR Sutton, E Agolini, M Rinelli, R Capolino, D Martinelli, G Zampino, M Dumić Show all
American Journal of Human Genetics | CELL PRESS | Published : 2019
Abstract
Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified ..
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Awarded by National Human Genome Research Institute
Funding Acknowledgements
This work was supported by the Australian Government National Health and Medical Research Council (program grant 1054618 and fellowship 1002098). P.J.L. was supported by the National Health and Medical Research Council (NHMRC) Career Development Fellowship GNT1032364. M.B. was supported by an NHMRC senior research fellowship (1102971) and an NHMRC program grant (1054618). Additional funding was provided by the Independent Research Institute Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Program. M.A.M. is a participant in the BIH Charite Junior Clinician Scientist Program funded by the Charite-Universitatsmediz in Berlin and the Berlin Institute of Health. V.R.S. receives support from the National Human Genome Research Institute (NHGRI) UM1 HG006542-07.C.D. and N.J.A. were supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (NIH-NINDS) R01 NS089791. M.M. was supported by the National Institute on Deafness and other Communicative Disorders (NIDCD) R01 DC09590.