MFN2 deletion of exons 7 and 8: founder mutation in the UK population

Abstract Mitofusin 2 (MFN2) 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 exon 7 and 8 resulting in nonsense mediated decay, segregating with disease when present in trans with another pathogenic MFN2 mutation. Detailed clinical and electrophysiological data on a series of five affected patients from four kindreds and, when available, their parents and relatives was collected. MFN2 Sanger sequencing, multiplex ligation probe amplification and haplotype analysis was 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 (4/5) and wheelchair dependency in childhood were common (4/5). All were compound heterozygous for a deletion of exon 7 and 8 in MFN2 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.
Source: Journal of the Peripheral Nervous System - Category: Neurology Authors: Tags: RESEARCH REPORT Source Type: research