A novel mutation in the GARS gene in a Malian family with Charcot‐Marie‐Tooth disease

Molecular Genetics & Genomic Medicine

卷:7

The H3Africa Consortium¹  Seybou H. Diallo²  Thomas Coulibaly²  Salimata Diarra²  Mohamed Keita²  Abdoulaye Yalcouyé²  Cheick O. Guinto²  Guida Landouré²  Oumar Samassékou²  Kenneth Fischbeck³  Dramane Coulibaly⁴  Salimata Diallo⁵  Lassana Cissé⁶ 

[1] ;

[2] Faculté de Médecine et d'Odontostomatologie USTTB Bamako Mali;

[3] Neurogenetics Branch, National Institutes of Neurological Disorders and Stroke Bethesda MD;

[4] Service de Médecine, Centre Hospitalier Universitaire Mère‐Enfant le "Luxembourg" BamakoMali;

[5] Service de Neurologie, Centre Hospitalier Universitaire Gabriel Touré Bamako Mali;

[6] Service de Neurologie, Centre Hospitalier Universitaire du Point “G” Bamako Mali;

关键词: CMT;    CMT2D;    GARS;    Mali;    novel mutation;   

DOI  :  10.1002/mgg3.782

来源: DOAJ

【 摘 要 】

Abstract Background Charcot‐Marie‐Tooth (CMT) disease is a very heterogeneous neurological condition with more than 90 reported genetic entities. It is the most common inherited peripheral neuropathy; however, cases are rarely reported in sub‐Saharan Africa. In addition, only few families, mostly of Caucasian ancestry, have been reported to have Charcot‐Marie‐Tooth disease type 2D (CMT2D) mutations. To date no case of CMT2D was reported in Africa. We present here a consanguineous family with CMT phenotype in which a novel mutation in the GARS (glycyl‐tRNA synthetase) gene was identified. Methods Patients were examined thoroughly and nerve conduction studies (NCS) were performed. DNA from the proband was used for CMT gene panel testing (including 50 genes, PMP22 duplication and mtDNA). Putative mutations were verified in all available family members to check for segregation. Results Two individuals, a male and a female, were found to be affected. Symptoms started in their teenage years with muscle weakness and atrophy in hands. Later, distal involvement of the lower limbs was noticed. Patients complained of minor sensory impairment. NCS showed no response in the upper as well as the lower limbs. Genetic testing surprisingly identified a novel heterozygous missense mutation c.794C>A (p.Ser265Tyr) in the GARS gene associated with CMT2D. This variant segregated with the disease in the family and was also seen in the mother who presented no symptoms. Conclusion This is the first report of a genetically confirmed CMT2D case in Africa, expanding its genetic epidemiology. Increasing access to genetic testing may reveal more novel CMT variants or genes in the African population that could be relevant to other populations and further our understanding of their mechanism.

【 授权许可】

Unknown