title: Identification of a novel splice site HSPG2 mutation and prenatal diagnosis in Schwartz Jampel Syndrome type 1 using whole exome sequencing.
abstract: Schwartz-Jampel Syndrome type 1 is a rare autosomal recessive musculoskeletal disorder (OMIM #255800) caused by various mutations in the HSPG2 gene encoding protein perlecan, a ubiquitous heparan sulfate proteoglycan, which is an integral component of basement membranes and possesses angiogenic and growth-promoting attributes primarily by acting as a co-receptor for the basic fibroblast growth factors in human body. We report a novel homozygous intronic 5' splice site mutation in this gene (c.4740 + 5G>A) in a child with clinical features of Schwartz-Jampel syndrome type 1. The mutation was detected by exome sequencing and later confirmed by Sanger sequencing. The mother was found to be heterozygous for the mutation and an ongoing pregnancy found to be unaffected. cDNA analysis revealed skipping of exon 37 of HSPG2 gene in the patient due to the splicing error caused by this mutation. This is likely to result in loss of 38 amino acids from the domain III of the perlecan protein and presumably affects its structure and function as per protein modeling predictions. This report demonstrates the utility of exome sequencing as a routine molecular diagnostic approach of choice for this rare disorder.
authors: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors: Aneek
authors: A
authors: Das Bhowmik
authors: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India; Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.
authors: Ashwin
authors: A
authors: Dalal
authors: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors: Divya
authors: D
authors: Matta
authors: Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, India.
authors: Rukmini M
authors: RM
authors: Kandadai
authors: Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, India.
authors: Meena A
authors: MA
authors: Kanikannan
authors: Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India; Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India. Electronic address: shagun.genetics@gmail.com.
authors: Shagun
authors: S
authors: Aggarwal
mesh_terms: D005091:Exons; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011296:Prenatal Diagnosis; D022821:RNA Splice Sites; D000073359:Exome Sequencing
chemical_list: D019812:Heparan Sulfate Proteoglycans; D022821:RNA Splice Sites; C071927:perlecan
keywords: Exome sequencing; HSPG2; Sanger sequencing; Schwartz-Jampel syndrome