Mutations in the consensus helicase domains of the Werner syndrome gene

摘要: Werner syndrome (WS) is an autosomal recessive disease with a complex phenotype that suggestive of accelerated aging. WS caused by mutations in gene, WRN, encodes predicted 1,432-amino-acid protein homology to DNA and RNA helicases. Previous work identified four the 3' end which resulted truncated products 1,060-1,247 amino acids but did not disrupt helicase domain region (amino 569-859). Here, additional subjects were screened for mutations, intron-exon structure gene was determined. A total 35 exons defined, coding sequences beginning second exon. Five new identified: two nonsense at codons 369 889; mutation splice-junction site, resulting 760 acids; 1-bp deletion causing frameshift; 391 acids. Another >15 kb genomic DNA, including 19-23; 1,186 long. Four these either partially or result completely missing region. These results confirm WRN are responsible WS. Also, location indicates presence absence does influence suggests complete loss function product.