Background and purpose The purpose was to provide an overview of genotype and phenotype distribution in a cohort of patients with Charcot–Marie–Tooth disease (CMT) and related disorders from central south China. Methods In all, 435 patients were enrolled and detailed clinical data were collected. Multiplex ligation‐dependent probe amplification for PMP22 duplication/deletion and CMT multi‐gene panel sequencing were performed. Whole exome sequencing was further applied in the remaining patients who failed to achieve molecular diagnosis. Results Among the 435 patients, 216 had CMT1, 14 had hereditary neuropathy with pressure palsies (HNPP), 178 had CMT2, 24 had distal hereditary motor neuropathy (dHMN) and three had hereditary sensory and autonomic neuropathy (HSAN). The overall molecular diagnosis rate was 70%: 75.7% in CMT1, 100% in HNPP, 64.6% in CMT2, 41.7% in dHMN and 33.3% in HSAN. The most common four genotypes accounted for 68.9% of molecular diagnosed patients. Relatively frequent causes were missense changes in PMP22 (4.6%) and SH3TC2 (2.3%) in CMT1; and GDAP1 (5.1%), IGHMBP2 (4.5%) and MORC2 (3.9%) in CMT2. Twenty of 160 detected pathogenic variants and the associated phenotypes have not been previously reported. Broad phenotype spectra were observed in six genes, amongst which the pathogenic variants in BAG3 and SPTLC1 were detected in two sporadic patients presenting with the CMT2 phenotype. Conclusions Our results provided a unique genotypic and phenotypic landscape of patients with CMT and related disorders from central south China, including a relatively high proportion of CMT2 and lower occurrence of PMP22 duplication. The broad phenotype spectra in certain genes have advanced our understanding of CMT.

<b><i>Introduction:</i></b> Rapid-onset dystonia parkinsonism (RDP), also referred to as Dystonia 12, is a rare autosomal dominant genetic disease characterized by abrupt onset of a rostrocaudal gradient of dystonia with prominent bulbar symptoms, and parkinsonian features, primarily bradykinesia and postural instability without tremor. The purpose of this study was to identify the genetic defect in a Chinese pedigree with familial RDP and to explore genotype-phenotype correlation. <b><i>Methods:</i></b> A 3-generation Chinese Han pedigree consisting of 9 members and 3 patients with RDP, and 200 unrelated ethnically matched normal subjects were recruited in this study. Exome sequencing was performed in the proband, and Sanger sequencing was then conducted in other family members and 200 normal controls. <b><i>Results:</i></b> In addition to the typical clinical manifestations of RDP, the proband and her sister presented tongue tremor which developed at the onset, and intriguingly the proband showed a “re-emergent” tongue tremor. Both the proband and her sister had a medical history of hyperthyroidism, and at the psychiatric interview they both received diagnoses of depression and anxiety. Excessive grammar errors existed in most sentences written by the proband, and this written-expression disorder occurred years before the onset of RDP. The mother of the proband presented tongue enlargement, oromandibular dystonia, and limb dystonia, which were not observed in her 2 daughters at the time of study. A missense variant, c.1838C&#x3e;T (p.T613M), in the <i>ATP1A3</i> gene, was identified in the 3 patients in the family and in 2 young children but was absent in family members without RDP and in the 200 normal controls. <b><i>Conclusion:</i></b> These findings may broaden the phenotypic spectrums of RDP with mutations in the <i>ATP1A3</i> gene, provide new insights into the diagnosis of RDP, and have implications for genetic counseling.

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