A novel WARS mutation (p.Asp314Gly) identified in a Chinese distal hereditary motor neuropathy family

Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies characterized by distal limb muscle wasting and weakness with no or minimal sensory abnormalities. To investigate the clinical and genetic features of dHMN caused by WARS mutations...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Clinical genetics 2019-08, Vol.96 (2), p.176-182
Hauptverfasser: Wang, Binghao, Li, Xiaobo, Huang, Shunxiang, Zhao, Huadong, Liu, Jun, Hu, Zhengmao, Lin, Zhiqiang, Liu, Lei, Xie, Yongzhi, Jin, Qingwen, Zhao, Huihui, Tang, Beisha, Niu, Qi, Zhang, Ruxu
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies characterized by distal limb muscle wasting and weakness with no or minimal sensory abnormalities. To investigate the clinical and genetic features of dHMN caused by WARS mutations in mainland China, we performed Sanger sequencing of the coding and untranslated region (UTR) regions of WARS in 160 unresolved dHMN and Charcot‐Marie‐Tooth (CMT) index patients. We detected a novel heterozygous variant c.941A>G (p.Asp314Gly) of WARS in an index patient from an autosomal dominant dHMN family including five affected members over three generations. The variant completely co‐segregates with the dHMN phenotype in the family, and it was classified as likely pathogenic according to the American College of Medical Genetics and Genomics standards and guidelines. The clinical features included juvenile to adult onset (15‐23 years), distal wasting and weakness, minimal sensory disturbance and length‐dependent motor axonal degeneration with CMT examination score ranging from 6 to 10. Our report further confirms the role of WARS in dHMN and indicates that the variant c.941A>G (p.Asp314Gly) of WARS is related to a mild to moderate affected and later onset phenotype of dHMN. Flow chart of our study. IPN, inherited peripheral neuropathy; dHMN, distal hereditary motor neuropathy; CMT1: demyelinating Charcot‐Marie‐Tooth disease; CMT2, axonal Charcot‐Marie‐Tooth disease; ACMG, American College of Medical Genetics and Genomics.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.13563