An inherited LMNA gene mutation in atypical Progeria syndrome
An inherited LMNA gene mutation in atypical Progeria syndrome
复制标题
DOI：
10.1002/ajmg.a.35557
复制
发表时间：
2012-11-01
影响因子：
2
通讯作者：
Sefiani, Abdelaziz
中科院分区：
文献类型：
--
作者：
Doubaj, Yassamine;De Sandre-Giovannoli, Annachiara;Sefiani, Abdelaziz
哈钦森吉尔福德早衰综合症 (HGPS) 是一种罕见的遗传性疾病，其特征是从儿童早期开始的多种临床特征，让人想起加速的衰老过程。 HGPS 的诊断基于对常见临床特征的识别以及对核纤层蛋白 A/C 编码基因 (LMNA) 外显子 11 内复发性杂合 c.1824C>T (p.Gly608Gly) 突变的检测。除了典型的 HGPS 之外，还描述了几种非典型早衰综合征 (APS)，其临床范围从下颌骨发育不良到非典型维尔纳综合征。这些患者的临床特征包括早衰症状，如身材矮小、突出的鼻子、头发过早变白、部分脱发、皮肤萎缩、脂肪营养不良、骨骼异常，如下颌发育不全和肢端骨质溶解，在某些情况下还伴有严重的动脉粥样硬化和代谢并发症。在一些情况下，APS 是由于除 p.Gly608Gly 之外的新杂合 LMNA 突变所致，或者是由于 NestorGuillermo 早衰综合征 (NGPS) 中的纯合 BAFN1 突变所致。我们在此报告并讨论一名非近亲摩洛哥患者出现非典型早衰症的观察结果。分子研究显示LMNA基因杂合突变c.412G>A (p.Glu138Lys)。这种突变以前被报道为从头突变，是从表现出体细胞嵌合体的表面健康的父亲遗传的。 (c) 2012 年 Wiley 期刊公司。
HutchinsonGilford Progeria syndrome (HGPS) is a rare genetic disorder, characterized by several clinical features that begin in early childhood, recalling an accelerated aging process. The diagnosis of HGPS is based on the recognition of common clinical features and detection of the recurrent heterozygous c.1824C>T (p.Gly608Gly) mutation within exon 11 in the Lamin A/C encoding gene (LMNA). Besides typical HGPS, several atypical progeria syndromes (APS) have been described, in a clinical spectrum ranging from mandibuloacral dysplasia to atypical Werner syndrome. These patients's clinical features include progeroid manifestations, such as short stature, prominent nose, premature graying of hair, partial alopecia, skin atrophy, lipodystrophy, skeletal anomalies, such as mandibular hypoplasia and acroosteolyses, and in some cases severe atherosclerosis with metabolic complications. APS are due in several cases to de novo heterozygous LMNA mutations other than the p.Gly608Gly, or due to homozygous BAFN1 mutations in NestorGuillermo Progeria syndrome (NGPS). We report here and discuss the observation of a non-consanguineous Moroccan patient presenting with atypical progeria. The molecular studies showed the heterozygous mutation c.412G>A (p.Glu138Lys) of the LMNA gene. This mutation, previously reported as a de novo mutation, was inherited from the apparently healthy father who showed a somatic cell mosaicism. (c) 2012 Wiley Periodicals, Inc.