A novel double mutation in cis in MFN2 causes Charcot-Marie-Tooth neuropathy type 2A

作者：Park Su Yeon; Kim So Yeon; Hong Yoon Ho; Cho Sung Im; Seong Moon Woo; Park Sung Sup

来源：Neurogenetics, 2012, 13(3): 275-280.

DOI：10.1007/s10048-012-0327-8

• MFN2
• Charcot-Marie-Tooth neuropathy
• Double mutation in cis
• Korean

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.

• 出版日期2012-8