POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria
POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria
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DOI：
10.1016/j.gene.2012.02.034
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发表时间：
2012-05-10
期刊：
影响因子：
3.5
通讯作者：
Dhar, Shweta U.
中科院分区：
文献类型：
--
作者：
Bekheirnia, Mir Reza;Zhang, Wei;Dhar, Shweta U.
POLG突变是迄今为止线粒体疾病最常见的核编码原因之一。携带POLG突变的个体表现出相当异质的临床表现，导致将这些患者分类为确定的临床表型的难度增加。本研究旨在探讨3-甲基戊烯二酸尿症患者线粒体细胞病变的分子基础，并扩大与POLG突变相关的临床表型，对1例23岁白人和拉丁美洲混血女性患者进行了临床、分子和遗传分析以及神经生理学检查，她在20岁时出现远端肌无力，在青春期发展为萎缩和卵巢发育不全。在尿有机酸分析中发现患者有3-甲基戊烯二酸和正常的3羟基异戊酸。进行POLG测序，发现杂合变体c.2851T>A（p.Y951N），预测其有害。3-甲基戊烯二酸尿症个体中POLG突变的报道有限。本病例报告的一名年轻女子与杂合子突变的POLG，提出了肌肉无力和萎缩，在年轻的时候，旨在帮助临床医生在类似的挑战性诊断的情况下，以及提高我们的理解POLG相关的疾病表型。由爱思唯尔公司出版
Mutations in POLG account for one of the most frequent nuclear encoded causes of mitochondrial disorders to date. Individuals harboring POLG mutations exhibit fairly heterogeneous clinical presentations leading to increasing difficulties in classifying these patients into defined clinical phenotypes. This study aims to investigate the molecular basis of a mitochondrial cytopathy in a patient with 3-methylglutaconic aciduria and to expand the clinical phenotype associated with POLG mutations.Clinical, molecular and genetic analyses as well as neurophysiological examinations were carried out for a 23-year-old woman of mixed Caucasian and Latin American ancestry with a history of cataracts diagnosed at age 1year, she had onset of distal muscle weakness at age 2years progressing to atrophy and ovarian dysgenesis at puberty. The patient was found to have 3-methylglutaconic acid with normal 3 hydroxyisovaleric acid on urine organic acid analysis. POLG sequencing was done and a heterozygous variant, c.2851T>A (p.Y951N) was found which is predicted to be deleterious. There are limited reports of POLG mutations in individuals with 3-methylglutaconic aciduria. This case report of a young woman with a heterozygous mutation in POLG, presenting with muscle weakness and atrophy at a young age aims to aid clinicians in similar challenging diagnostic situations as well as enhances our understanding of POLG-related disease phenotypes. Published by Elsevier B.V.