Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May 22;78(21):1644-9.
doi: 10.1212/WNL.0b013e3182574f8f. Epub 2012 May 9.

Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy

Z Zhao  1 , A Hashiguchi, J Hu, Y Sakiyama, Y Okamoto, S Tokunaga, L Zhu, H Shen, H Takashima
Affiliations

Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy

Z Zhao et al. Neurology. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Pedigree of the distal hereditary motor neuropathy family
The arrow indicates the proband. Affected individuals are represented by solid black symbols; open symbols represent healthy individuals.
Figure 2
Figure 2. Clinical, radiologic, and genetic findings of the distal hereditary motor neuropathy family
(A) A picture of patient 1 shows moderate pes cavus and toe clawing. (B) A picture of patient 2 shows pes cavus. (C and D) Axial T1-weighted images of the lower limbs in patient 1. (C) Axial image of the thighs, illustrating marked fatty replacement of the vastus lateralis muscle (arrows). (D) Axial image of the legs demonstrating complete fatty replacement of the gastrocnemius muscle (arrowheads). (E and F) Axial T1-weighted images of the lower limbs of a healthy control subject. (G) Chromatogram of the heterozygous c.2677G>A (p.D893N) mutation in exon 19 of AARS: left, 4 affected members; right, 4 unaffected relatives. (H) Comparison of AARS from different species. Arrowhead (▾) on top of the alignment indicates 893 amino acids.
See this image and copyright information in PMC

References

    1. Harding AE. Inherited neuronal atrophy and degeneration predominantly of lower motor neurons. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. Philadelphia: WB Saunders; 1993
    1. Drew AP, Blair IP, Nicholson GA. Molecular genetics and mechanisms of disease in distal hereditary motor neuropathies: insights directing future genetic studies. Curr Mol Med 2011;11:650–665 - PubMed
    1. Irobi J, Van Impe K, Seeman P, et al. Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. Nat Genet 2004;36:597–601 - PubMed
    1. Houlden H, Laura M, Wavrant-De Vrièze F, et al. Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2. Neurology 2008;71:1660–1668 - PubMed
    1. Antonellis A, Ellsworth RE, Sambuughin N, et al. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet 2003;72:1293–1299 - PMC - PubMed

Publication types

Substances