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

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.

Novel GDAP1 Mutation in a Vietnamese Family with Charcot-Marie-Tooth Disease.

BACKGROUND: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth (CMT) disease and over 80 different mutations have been identified so far. This study analyzed the clinical and genetic characteristics of a Vietnamese CMT family that was affected by a novel GDAP1 mutation. METHODS: We present three children of a family with progressive weakness, mild sensory loss, and absent tendon reflexes. Electrodiagnostic analyses displayed an axonal type of neuropathy in affected patients. Sequencing of GDAP1 gene was requested for all members of the family. RESULTS: All affected individuals manifested identical clinical symptoms of motor and sensory impairments within the first three years of life, and nerve conduction study indicated the axonal degeneration. A homozygous GDAP1 variant (c.667_671dup) was found in the three affected children as recessive inheritance pattern. The mutation leads to a premature termination codon that shortens GDAP1 protein (p.Gln224Hisfs∗37). Further testing showed heterozygous c.667_671dup variant in the parents. DISCUSSION: Our study expands the mutational spectrum of GDAP1-related CMT disease with the new and unreported GDAP1 variant. Alterations in GDAP1 gene should be evaluated as CMT causing variants in the Vietnamese population, predominantly axonal form of neuropathy in CMT disease.