Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth DiseaseReportar como inadecuado




Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease CMT type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive.

Methodology and Principal Findings

Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability.

Conclusion

GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.



Autor: Yi-Chu Liao, Yo-Tsen Liu, Pei-Chien Tsai, Chia-Ching Chang, Yen-Hua Huang, Bing-Wen Soong, Yi-Chung Lee

Fuente: http://plos.srce.hr/



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