Dataset Information

Genotype-phenotype characteristics of Vietnamese patients diagnosed with Charcot-Marie-Tooth disease.

ABSTRACT:

Background

Charcot-Marie-Tooth (CMT) disease is one of the most common hereditary neuropathies. Identifying causative mutations in CMT is essential as it provides important information for genetic diagnosis and counseling. However, genetic information of Vietnamese patients diagnosed with CMT is currently not available.

Methods

In this study, we described the clinical profile and determined the mutation spectrum of CMT in a cohort of Vietnamese patients with CMT by using a combination of multiplex ligation-dependent probe amplification and next-generation sequencing targeting 11 genes PMP22, MPZ, EGR2, NEFL, MFN2, GDAP1, GARS, MTMR2, GJB1, RAB7A, LITAF.

Results

In 31 CMT cases, the mutation detection rate was 42% and the most common genetic aberration was PMP22 duplication. The pedigree analysis showed two de novo mutations c.64C > A (p.P22T) and c.281delG (p.G94Afs*17) in the NEFL and PMP22 genes, respectively.

Conclusion

The results of this study once again emphasize the important role of molecular diagnosis and provide preliminary genetic data on Vietnamese patients with CMT.

SUBMITTER: Nguyen-Le TH

PROVIDER: S-EPMC9480926 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Genotype-phenotype characteristics of Vietnamese patients diagnosed with Charcot-Marie-Tooth disease.

Nguyen-Le Trung-Hieu TH Do Minh Duc MD Le Linh Hoang Gia LHG Nhat Quynh Nhu Nguyen QNN Hoang Nghia Trong Tien NTT Van Le Tuan T Mai Thao Phuong TP

Brain and behavior 20220808 9

<h4>Background</h4>Charcot-Marie-Tooth (CMT) disease is one of the most common hereditary neuropathies. Identifying causative mutations in CMT is essential as it provides important information for genetic diagnosis and counseling. However, genetic information of Vietnamese patients diagnosed with CMT is currently not available.<h4>Methods</h4>In this study, we described the clinical profile and determined the mutation spectrum of CMT in a cohort of Vietnamese patients with CMT by using a combina ...[more]

PMID: 35938991

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Project description:Charcot-Marie-Tooth type 4 (CMT4) is an autosomal recessive severe form of neuropathy with genetic heterogeneity. CMT4B1 is caused by mutations in the myotubularin-related 2 (MTMR2) gene and as a member of the myotubularin family, the MTMR2 protein is crucial for the modulation of membrane trafficking. To enable future clinical trials, we performed a detailed review of the published cases with MTMR2 mutations and describe four novel cases identified through whole-exome sequencing (WES). The four unrelated families harbor novel homozygous mutations in MTMR2 (NM_016156, Family 1: c.1490dupC; p.Phe498IlefsTer2; Family 2: c.1479+1G>A; Family 3: c.1090C>T; p.Arg364Ter; Family 4: c.883C>T; p.Arg295Ter) and present with CMT4B1-related severe early-onset motor and sensory neuropathy, generalized muscle atrophy, facial and bulbar weakness, and pes cavus deformity. The clinical description of the new mutations reported here overlap with previously reported CMT4B1 phenotypes caused by mutations in the phosphatase domain of MTMR2, suggesting that nonsense MTMR2 mutations, which are predicted to result in loss or disruption of the phosphatase domain, are associated with a severe phenotype and loss of independent ambulation by the early twenties. Whereas the few reported missense mutations and also those truncating mutations occurring at the C-terminus after the phosphatase domain cause a rather mild phenotype and patients were still ambulatory above the age 30 years. Charcot-Marie-Tooth neuropathy and Centronuclear Myopathy causing mutations have been shown to occur in proteins involved in membrane remodeling and trafficking pathway mediated by phosphoinositides. Earlier studies have showing the rescue of MTM1 myopathy by MTMR2 overexpression, emphasize the importance of maintaining the phosphoinositides equilibrium and highlight a potential compensatory mechanism amongst members of this pathway. This proved that the regulation of expression of these proteins involved in the membrane remodeling pathway may compensate each other's loss- or gain-of-function mutations by restoring the phosphoinositides equilibrium. This provides a potential therapeutic strategy for neuromuscular diseases resulting from mutations in the membrane remodeling pathway.

Dataset Information

Genotype-phenotype characteristics of Vietnamese patients diagnosed with Charcot-Marie-Tooth disease.

Background

Methods

Results

Conclusion

Publications

Genotype-phenotype characteristics of Vietnamese patients diagnosed with Charcot-Marie-Tooth disease.

Similar Datasets

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