WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations.
WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations.
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DOI：
10.1007/s00439-010-0832-5
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发表时间：
2010-07
期刊：
影响因子：
5.3
通讯作者：
Oshima J
中科院分区：
文献类型：
--
作者：
Friedrich K;Lee L;Leistritz DF;Nürnberg G;Saha B;Hisama FM;Eyman DK;Lessel D;Nürnberg P;Li C;Garcia-F-Villalta MJ;Kets CM;Schmidtke J;Cruz VT;Van den Akker PC;Boak J;Peter D;Compoginis G;Cefle K;Ozturk S;López N;Wessel T;Poot M;Ippel PF;Groff-Kellermann B;Hoehn H;Martin GM;Kubisch C;Oshima J
Werner综合征（WS）是一种常染色体隐性节段性类早衰综合征，由编码DNA解旋酶RecQ家族成员的WRN位点零突变引起。自1988年以来，国际沃纳综合征登记处从全球110个谱系中登记了130例分子确诊的WS病例。我们现在报告了18个新的突变，包括两个基因组重排，一个导致新的外显子的深内含子突变，一个导致利用附近剪接位点的剪接一致突变，以及两个罕见的错义突变。我们还回顾了不同种族/地理群体之间创始人突变的证据。之前在日本和北撒丁岛报道过创始人WRN突变。我们的登记处现在表明，特征性突变起源于摩洛哥、土耳其、荷兰和其他地方。
Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere.