Ethnic‐specific WRN mutations in South Asian Werner syndrome patients: potential founder effect in patients with Indian or Pakistani ancestry

Abstract W erner syndrome ( WS ) 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 J apan and S ardinia, such mutations have not been previously described among patients of S outh A sian descent. Here, we report two novel WRN mutations in three pedigrees. A homozygous c.561A>G mutation in exon 6 was identified both in a pedigree from K erala, I ndia and in a B ritish patient of P akistani ancestry. Although c.561A>G does not alter the corresponding amino acid (p.Lys187), it creates a cryptic splice site resulting in a 98 bp deletion at the mRNA level (r.557_654del98) followed by a frameshift (p.Lys187Trpfs*13). These two cases shared the same haplotype across the WRN gene, and were distinct from another I ndian W erner patient with a homozygous stop codon mutation, c.2855 C > A (p.Ser952*), in exon 24. As the I ndian population increases and the awareness of WS grows, we anticipate that more cases will be identified with these founder mutations among S outh A sian WS patients.