POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria

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• 作者：Mir Reza Bekheirnia^a ; Wei Zhang^a ; Tanya Eble^a ; Alecia Willis^a ; Aziz Shaibani^b ; ^c ; Lee-Jun C. Wong^a ; Fernando Scaglia^a ; Shweta U. Dhar^a ; ^b ; ^dhar@bcm.edu
• 关键词：POLG ; Polymerase gamma ; MRI ; Magnetic resonance imaging ; EKG ; Electrocardiogram ; EEG ; Electroencephalogram ; GALT ; Galactose-1-phosphate uridylyltransferase ; GJB1 ; Gap junction beta-1 ; MPZ ; Myelin protein zero ; DNA ; Deoxyribose nucleic acid ; STR ; Short tan
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：10 May, 2012
• 卷：499
• 期：1
• 页码：209-212
• 文件大小：299 K

摘要

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.