Premium
Axonal Charcot‐Marie‐Tooth neuropathy concurrent with distal and proximal weakness by translational elongation of the 3′ UTR in NEFH
Author(s) -
Nam Da Eun,
Jung SungChul,
Yoo Da Hye,
Choi Sun Seong,
Seo SungYum,
Kim Gwang Hoon,
Kim Song Ja,
Nam Soo Hyun,
Choi ByungOk,
Chung Ki Wha
Publication year - 2017
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns.12223
Subject(s) - weakness , medicine , anatomy
Abstract Mutations in the NEFH gene encoding the heavy neurofilament protein are usually associated with neuronal damage and susceptibility to amyotrophic lateral sclerosis (ALS). Recently, frameshift variants in NEFH (p.Asp1004Glnfs*58 and p.Pro1008Alafs*56) have been reported to be the underlying cause of axonal Charcot‐Marie‐Tooth disease type 2CC (CMT2CC). The frameshift mutation resulted in a stop loss and translation of a cryptic amyloidogenic element (CAE) encoded by the 3′ untranslated region (UTR). This study also identified a de novo c.3015_3027dup frameshift mutation predicting p.Lys1010Glnfs*57 in NEFH from a CMT2 family with an atypical clinical symptom of prominent proximal weakness. This mutation is located near the previously reported frameshift mutations, suggesting a mutational hotspot. Lower limb magnetic resonance imaging (MRI) revealed marked hyperintense signal changes in the thigh muscles compared with those in the calf muscles. Therefore, this study suggests that the stop loss and translational elongations by the 3′ UTR of the NEFH mutations may be a relatively frequent genetic cause of axonal peripheral neuropathy with the specific characteristics of proximal dominant weakness.