Molecular basis of Kindler syndrome in Italy: novel and recurrent Alu/Alu recombination, splice site, nonsense, and frameshift mutations in the KIND1 gene.
Molecular basis of Kindler syndrome in Italy: novel and recurrent Alu/Alu recombination, splice site, nonsense, and frameshift mutations in the KIND1 gene.
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意大利金德勒综合征的分子基础：KIND1 基因中的新型和复发性 Alu/Alu 重组、剪接位点、无义突变和移码突变。
DOI：
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发表时间：
2006
影响因子：
6.5
通讯作者：
D. Castiglia
中科院分区：
文献类型：
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作者：
C. Has;V. Wessagowit;M. Pascucci;Corinna Baer;B. Didona;C. Wilhelm;C. Pedicelli;A. Locatelli;J. Kohlhase;G. Ashton;G. Tadini;G. Zambruno;L. Bruckner;J. McGrath;D. Castiglia
金德勒综合征（KS）是一种罕见的常染色体隐性遗传疾病，其特征是儿童期皮肤起泡，随后出现光敏性和进行性皮肤色素异常。大多数KS病例是由编码kindlin-1的KIND 1基因突变引起的，kindlin-1是角质形成细胞中局灶性粘连的一种成分。在这里，我们报告的新的和复发的KIND 1基因突变在9个无关的意大利KS个人。一个新的基因组缺失约3.9 kb的4例患者来自同一个意大利地区。该突变从KIND 1 mRNA中删除外显子10和11，导致截短的kindlin-1。缺失断裂点嵌入在EASX重复序列中，特别是在相同的30 bp序列中，表明EASX介导的同源重组为致病机制。KIND 1单倍型分析表明，这种大缺失的患者与祖先有关。另外五个突变被公开，其中两个是新的。迄今为止，在意大利患者中已发现四种复发性突变，约占该人群中KS等位基因的75%。KIND 1内含子区域中重复元件的丰度以及大缺失的鉴定表明，基因组重排可能是导致显著比例KS病例的原因。这一发现对KS个体的最佳KIND 1突变筛查具有影响。
Kindler syndrome (KS) is a rare autosomal recessive disorder characterized by skin blistering in childhood followed by photosensitivity and progressive poikiloderma. Most cases of KS result from mutations in the KIND1 gene encoding kindlin-1, a component of focal adhesions in keratinocytes. Here, we report novel and recurrent KIND1 gene mutations in nine unrelated Italian KS individuals. A novel genomic deletion of approximately 3.9 kb was identified in four patients originating from the same Italian region. This mutation deletes exons 10 and 11 from the KIND1 mRNA leading to a truncated kindlin-1. The deletion breakpoint was embedded in AluSx repeats, specifically in identical 30-bp sequences, suggesting Alu-mediated homologous recombination as the pathogenic mechanism. KIND1 haplotype analysis demonstrated that patients with this large deletion were ancestrally related. Five additional mutations were disclosed, two of which were novel. To date, four recurrent mutations have been identified in Italian patients accounting for approximately approximately 75% of KS alleles in this population. The abundance of repetitive elements in intronic regions of KIND1, together with the identification of a large deletion, suggests that genomic rearrangements could be responsible for a significant proportion of KS cases. This finding has implications for optimal KIND1 mutational screening in KS individuals.
Herlitz 交界性大疱性表皮松解症患者 LAMC2 基因中的一种新的纯合无义突变。
影响因子：
3.5
作者：
Baudoin,C;Miquel,C;Gagnoux-Palacios,L;Pulkkinen,L;Christiano,AM;Uitto,J;Tadini,G;Ortonne,JP;Meneguzzi,G
通讯作者：
Meneguzzi,G
影响因子：
9.8
作者：
Le Saux, O;Beck, K;Boyd, CD
通讯作者：
Boyd, CD
影响因子：
9.8
作者：
Ringpfeil, F;Nakano, A;Pulkkinen, L
通讯作者：
Pulkkinen, L