A cohort study of MFN2 mutations and phenotypic spectrums in Charcot–Marie–Tooth disease 2A patients. (18th June 2014)

• Record Type: Journal Article
• Authors: Choi, B.‐O.; Nakhro, K.; Park, H.J.; Hyun, Y.S.; Lee, J.H.; Kanwal, S.; Jung, S.‐C.; Chung, K.W.
• Is Part Of: Clinical genetics. Volume 87:Number 6(2015:Jun.)
• Page Start: 594
• Page End: 598
• Publication Date: 2014-06-18
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12432
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12432-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12432-para-0001">Charcot–Marie–Tooth disease 2A (CMT2A) is the most common axonal form of peripheral neuropathy caused by a defect in the <italic>mitofusin 2</italic> (<italic>MFN2</italic>) gene, which encodes an outer mitochondrial membrane GTPase. <italic>MFN2</italic> mutations result in a large range of phenotypes. This study analyzed the prevalence of <italic>MFN2</italic> mutation in Korean families with their assorted phenotypes (607 CMT families and 160 CMT2 families). Direct sequencing of the <italic>MFN2</italic> coding exons or whole‐exome sequencing has been applied to identify causative mutations. A total of 21 mutations were found in 36 CMT2 families. Comparative genotype–phenotype correlations impacting severity, onset age, and specific symptoms were assessed. Most mutations were seen in the GTPase domain (∼86%). A deletion mutation found in the transmembrane helices is reported for the first time, as well as five novel mutations at other domains. <italic>MFN2</italic> mutations made up 5.9% of total CMT families, whereas 22.9% in CMT2 families, of which 27.8% occurred <italic>de novo</italic>. Interestingly, patient phenotypes ranged from mild to severe even for the same mutation, suggesting other factors influenced phenotype and penetrance. This CMT2A cohort study will be useful for molecular diagnosis and treatment of axonal neuropathy.</p> </abstract>