Genetic and clinical features of Chinese patients with mitochondrial ataxia identified by targeted next‐generation sequencing

Abstract

Our results implicate that mitochondrial ataxia might not be as rare in Chinese as previously assumed. This study firstly defines the mutations of mitochondrial ataxia in a Chinese population by targeted NGS, which broadens the clinical spectrum of mtDNA mutations and highlights the importance of screening mtDNA and nDNA mutations among undefined ataxia patients.

Genetic spectrum and clinical profiles in a southeast Chinese cohort of Charcot‐Marie‐Tooth disease

“…Owing to CMT's clinical and genetic heterogeneity, it is expensive and time‐consuming to screen all the possible causative genes using conventional Sanger sequencing. However, highthroughput targeted next‐generation sequencing (NGS) has been employed successfully in CMT and other neurogenetic diseases such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP), and hereditary ataxia (HA) . Consequently, nearly 90 genes associated with CMT and other inherited peripheral neuropathies have been assembled in a gene panel, and parallel sequencing can be performed to interrogate these genes.…”

“…However, highthroughput targeted next-generation sequencing (NGS) has been employed successfully in CMT 9,10 and other neurogenetic diseases such as amyotrophic lateral sclerosis (ALS), [11][12][13] hereditary spastic paraplegia (HSP), 14,15 and hereditary ataxia (HA). 16,17 Consequently, nearly 90 genes associated with CMT and other inherited peripheral neuropathies have been assembled in a gene panel, and parallel sequencing can be performed to interrogate these genes. Patients were evaluated and diagnosed by at least two senior neurologists according to the strategy described in our previous reports.…”

Mitochondrial ataxia is genetically and phenotypically heterogeneous

“…With interest, we read the article by Dong et al about the genetic cause of ataxia in 33 Chinese patients. 1 The included patients were investigated by next-generation sequencing (NGS) for a possible genetic cause of the clinical presentation. 1 The study raises a number of comments and concerns.…”

“…Finally, we do not agree with the statement that there is no gold standard for assessing the pathogenicity of a mutation. 1 At least for tRNA variants, the pathogenicity can be easily assessed by application of the modified Yarham score. 14 The strength of the genotypephenotype correlation can be assessed by application of the Smith score.…”