Ethnic-Specific WRN Mutations in South Asian Werner Syndrome Patients: Potential Founder Effect in Patients with Indian or Pakistani Ancestry.

[werner syndrome]

Werner syndrome is a rare autosomal recessive disorder characterized by multiple features consistent with accelerated aging . It is caused by mutations in the WRN gene , which encodes a RecQ type helicase . To date , more than 70 disease-causing mutations have been reported . While founder mutations and a corresponding relatively high incidence of WS have been reported in Japan and Sardinia , such mutations have not been previously described among patients of South Asian descent . Here we report two novel WRN mutations in three pedigrees . A homozygous c .561 A >G mutation in exon 6 was identified both in a pedigree from Kerala , India and in a British patient of Pakistani ancestry . Although c .561 A >G does not alter the corresponding amino acid (p .K 187 K ), it creates a cryptic splice site resulting in a 98 bp deletion at the mRNA level (r .557 -654 del 98 ) followed by a frameshift (p .K 187 fs ). These two cases shared the same haplotype across the WRN gene , and were distinct from another Indian Werner patient with a homozygous stop codon mutation , c .2855 C >A (p .S 952 *) in exon 24 . As the Indian population increases and the awareness of Werner syndrome grows , we anticipate that more cases will be identified with these founder mutations among South Asian Werner syndrome patients .