A novel splice-site mutation of WRN (c.IVS28+2T>C) identified in a consanguineous family with Werner Syndrome

Werner Syndrome (WS) is a rare, adult‑onset progeroid syndrome that is associated with multiple age‑associated complications and relatively short life expectancy. The characteristics of WS include a 'bird‑like' appearance, canities, cataracts and ulcerations around the ankles. In addition, certain patients develop hypogonadism with atrophic genitalia and infertility. The average life span of affected individuals is 54 years. Previous studies have demonstrated that mutations in the Werner syndrome RecQ like helicase gene (WRN) may contribute to WS. The present study investigated a consanguineous family with WS, comprising of 4 generations from Northwest China (Gansu province). A novel homozygous splice‑site mutation in WRN (c.IVS28+2T>C) was identified in this family and was predicted to be deleterious. No further relevant mutations were identified by direct sequencing of the genes lamin A/C, barrier to autointegration factor 1, zinc metallopeptidase STE24 and DNA polymerase Δ1. cDNA sequencing and alignments were performed to further confirm the pathogenicity of this mutation. The results support the important role of WRN in WS and expand the spectrum of known WRN mutations. In addition, it may provide novel approaches in genetic diagnosis and counseling of families with WS.