RT Journal Article
SR Electronic
T1 Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 1644
OP 1649
DO 10.1212/WNL.0b013e3182574f8f
VO 78
IS 21
A1 Z. Zhao
A1 A. Hashiguchi
A1 J. Hu
A1 Y. Sakiyama
A1 Y. Okamoto
A1 S. Tokunaga
A1 L. Zhu
A1 H. Shen
A1 H. Takashima
YR 2012
UL http://n.neurology.org/content/78/21/1644.abstract
AB Objective: To identify a new genetic cause of distal hereditary motor neuropathy (dHMN), which is also known as a variant of Charcot-Marie-Tooth disease (CMT), in a Chinese family. Methods: We investigated a Chinese family with dHMN clinically, electrophysiologically, and genetically. We screened for the mutations of 28 CMT or related pathogenic genes using an originally designed microarray resequencing DNA chip. Results: Investigation of the family history revealed an autosomal dominant transmission pattern. The clinical features of the family included mild weakness and wasting of the distal muscles of the lower limb and foot deformity, without clinical sensory involvement. Electrophysiologic studies revealed motor neuropathy. MRI of the lower limbs showed accentuated fatty infiltration of the gastrocnemius and vastus lateralis muscles. All 4 affected family members had a heterozygous missense mutation c.2677G>A (p.D893N) of alanyl-tRNA synthetase (AARS), which was not found in the 4 unaffected members and control subjects. Conclusion: An AARS mutation caused dHMN in a Chinese family. AARS mutations result in not only a CMT phenotype but also a dHMN phenotype. AARS=alanyl-tRNA synthetase; CMT=Charcot-Marie-Tooth; dHMN=distal hereditary motor neuropathy; MRC=Medical Research Council; SCV=sensory nerve conduction velocity