doi:10.1038/nindia.2016.158 Published online 29 November 2016
Scientists in Jammu and Kashmir (J&K) have identified an extremely rare severe skeletal disorder – Progressive Pseudorheumatoid Dysplasia1 – in the strife-torn northern state of India, where the rate of consanguinity (or marriages between blood relatives) is relatively high.
The disorder, with a reported incidence of one in a million in the UK, remained unidentified for decades in the remote lower Himalayan village of Arai in the Poonch district of J&K. “Until recently the village was inaccessible by modern transportation,” says Swarkar Sharma, one of the researchers from the Human Genetics Research Group, Department of Biotechnology at Shri Mata Vaishno Devi University in Katra, J&K.
Since the cause of the disease was unknown and there was no means to manage it, this otherwise rare disorder has crippled large number of villagers in recent years. In the absence of medical intervention and because of its severity, the disorder handicaps people for life.
Using pedegree analysis of the families, radiological screening and next generation sequencing technologies (Whole Exome Sequencing), Sharma and colleagues identified two mutations – one reported for the first time – in the gene WISP3 as the cause of the disease in the village.
The genetic characterization, the scientists believe, will aid in genetic counseling and management, critically required to curb this rare disorder.
Consanguinity due to restricted geographical localization, endogamous population groups and high inbreeding leads to a very high prevalence of several rare human genetic disorders, yet to be identified. These disorders might have remained unidentified due to geographical isolation, less awareness and limited clinical resources, the researchers say.
1. Rai, A. et al. Whole exome screening identifies novel and recurrent WISP3 mutations causing Progressive Pseudorheumatoid Dysplasia in Jammu and Kashmir-India. Sci. Rep. (2016) doi: 10.1038/srep27684