title: A novel double mutation in cis in MFN2 causes Charcot-Marie-Tooth neuropathy type 2A.
abstract: Mutations in mitofusin-2 (MFN2) are the most common cause of axonal Charcot-Marie-Tooth (CMT) neuropathy. Herein, we report a novel double mutation in cis (c.[474+4A>G; 668T>A]) in a Korean family with late-onset autosomal dominant mild axonal CMT. Transcriptional analysis demonstrated aberrant splicing with exon 5 skipping and premature termination of translation before the missense mutation in exon 7. Interestingly, the aberrant splicing was incomplete, with some of the primary transcripts being spliced correctly and expressing the downstream missense mutation. The pathogenic relevance of the missense mutation would not be appreciated without the leaky aberrant splicing and the insensitivity of MFN2 to haploinsufficiency.
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Yoon-Ho
authors.initials: YH
authors.lastname: Hong
authors.forename: Sung Im
authors.initials: SI
authors.lastname: Cho
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D004594:Electrophysiology / Q000379:methods; D005091:Exons; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D008967:Molecular Biology; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human