Ethnic-Specific WRN Mutations in South Asian Werner Syndrome Patients: Potential Founder Effect in Patients with Indian or Pakistani Ancestry.
Werner syndrome is a rare autosomal recessive disorder characterized by multiple features consistent with accelerated aging. It is caused by mutations in theWRNgene, 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 novelWRNmutations in three pedigrees. A homozygous c.561A>G mutation in exon 6 was identified both in a pedigree from Kerala, India and in a British patient of Pakistani ancestry. Although c.561A>G does not alter the corresponding amino acid (p.K187K), it creates a cryptic splice site resulting in a 98bp deletion at the mRNA level (r.557-654del98) followed by a frameshift (p.K187fs). These two cases shared the same haplotype across theWRNgene, and were distinct from another Indian Werner patient with a homozygous stop codon mutation, c.2855 C>A (p.S952*) 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.
Department of Pathology and Division of Medical Genetics, University of Washington, Seattle, WA, USA.
Bidisha
B
Saha
Davor
D
Lessel
Sheela
S
Nampoothiri
Anuradha S
AS
Rao
Fuki M
FM
Hisama
Dincy
D
Peter
Chris
C
Bennett
Gudrun
G
Nürnberg
Peter
P
Nürnberg
George M
GM
Martin
Christian
C
Kubisch
Junko
J
Oshima
India; Pakistan; WRN; Werner syndrome; founder mutations; segmental progeroid syndromes