Whole Exome Screening Identifies Novel and Recurrent WISP3 Mutations Causing Progressive Pseudorheumatoid Dysplasia in Jammu and Kashmir-India.

Sci Rep 2016 06 13;6:27684. Epub 2016 Jun 13.

Human Genetics Research Group, Department of Biotechnology, Shri Mata Vaishno Devi University, Katra, J&K, India.

We report identification and genetic characterization of a rare skeletal disorder that remained unidentified for decades in a village of Jammu and Kashmir, India. The population residing in this region is highly consanguineous and a lack of understanding of the disorder has hindered clinical management and genetic counseling for the many affected individuals in the region. We collected familial information and identified two large extended multiplex pedigrees displaying apparent autosomal recessive inheritance of an uncharacterized skeletal dysplasia. Whole exome sequencing (WES) in members of one pedigree revealed a rare mutation in WISP3:c.156C > A (NP_003871.1:p.Cys52Ter), that perfectly segregated with the disease in the family. To our surprise, Sanger sequencing the WISP3 gene in the second family identified a distinct, novel splice site mutation c.643 + 1G > A, that perfectly segregated with the disease. Combining our next generation sequencing data with careful clinical documentation (familial histories, genetic data, clinical and radiological findings), we have diagnosed the families with Progressive Pseudorheumatoid Dysplasia (PPD). Our results underscore the utility of WES in arriving at definitive diagnoses for rare skeletal dysplasias. This genetic characterization will aid in genetic counseling and management, critically required to curb this rare disorder in the families.

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep27684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904372PMC
June 2016
31 Reads

Publication Analysis

Top Keywords

rare skeletal
8
progressive pseudorheumatoid
8
pseudorheumatoid dysplasia
8
genetic characterization
8
perfectly segregated
8
segregated disease
8
genetic counseling
8
genetic
5
disease family
4
sanger sequencing
4
family surprise
4
surprise sanger
4
wisp3 gene
4
distinct novel
4
novel splice
4
splice site
4
site mutation
4
identified distinct
4
family identified
4
np_0038711pcys52ter perfectly
4

References

(Supplied by CrossRef)

H Hamamy et al.
J Community Genet 2012

C Gilissen et al.
Genome biology 2011

X Zhu et al.
Genet Med 2015

MJ Bamshad et al.
Nature reviews. Genetics 2011

KM Boycott et al.
Nature reviews. Genetics 2013

MA DePristo et al.
Nature genetics 2011

MJ Landrum et al.
Nucleic acids research 2014

A Dalal et al.
American journal of medical genetics. Part A 2012

JR Hurvitz et al.
Nature genetics 1999

R Wynne-Davies et al.
The Journal of bone and joint surgery. British volume 1982

AV Ekbote et al.
Seminars in arthritis and rheumatism 2013

Similar Publications