MFN2 deletion of exons 7 and 8: founder mutation in the UK population. Issue 2 (June 2015)

• Record Type: Journal Article
• Authors: Carr, Aisling S.; Polke, James M.; Wilson, Jacob; Pelayo‐Negro, Ana L.; Laura, Matilde; Nanji, Tina; Holt, James; Vaughan, Jennifer; Rankin, Julia; Sweeney, Mary G.; Blake, Julian; Houlden, Henry; Reilly, Mary M.
• Is Part Of: Journal of the peripheral nervous system. Volume 20:Issue 2(2015)
• Page Start: 67
• Page End: 71
• Publication Date: 2015-06
• Subjects: Nervous system -- Periodicals; Nerves, Peripheral -- Diseases -- Periodicals; Peripheral Nervous System Diseases -- Periodicals; Peripheral Nervous System -- Periodicals; 612.81
• DOI: 10.1111/jns.12117
• Languages: English
• ISSNs: 1085-9489

Abstract

<abstract abstract-type="main" id="jns12117-abs-0001"> <title>Abstract</title> <p id="jns12117-para-0001">Mitofusin 2 (<italic>MFN2</italic>) mutations are the most common cause of axonal Charcot‐Marie‐Tooth disease (CMT2). The majority are inherited in an autosomal dominant manner but recessive and semi‐dominant kindreds have also been described. We previously reported a deletion of exons 7 and 8 resulting in nonsense‐mediated decay, segregating with disease when present <italic>in trans</italic> with another pathogenic <italic>MFN2</italic> mutation. Detailed clinical and electrophysiological data on a series of five affected patients from four kindreds and, when available, their parents and relatives were collected. <italic>MFN2</italic> Sanger sequencing, multiplex ligation probe amplification, and haplotype analysis were performed. A severe early‐onset CMT phenotype was seen in all cases: progressive distal weakness, wasting, and sensory loss from infancy or early childhood. Optic atrophy (four of five) and wheelchair dependency in childhood were common (four of five). All were compound heterozygous for a deletion of exons 7 and 8 in <italic>MFN2</italic> with another previously reported pathogenic mutation (Phe216Ser, Thr362Met, and Arg707Trp). Carrier parents and relatives were unaffected (age range: 24–82 years). Haplotype analysis confirmed that the deletion had a common founder in all families.</p> </abstract>