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.
Background and Objectives: Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies. The objectives of this study were to report the clinical and genetic features of dHMN patients in a Chinese cohort.Aims and Methods: We performed clinical assessments and whole-exome sequencing in 24 dHMN families from Mainland China. We conducted a retrospective analysis of the data and investigated the frequency and clinical features of patients with a confirmed mutation.Results: Two novel heterozygous mutations in GARS, c.373G>C (p.E125Q) and c.1015G>A (p.G339R), were identified and corresponded to the typical dHMN-V phenotype. Together with families with WARS, SORD, SIGMAR1, and HSPB1 mutations, 29.2% of families (7/24) acquired a definite genetic diagnosis. One novel heterozygous variant of uncertain significance, c.1834G>A (p.G612S) in LRSAM1, was identified in a patient with mild dHMN phenotype.Conclusion: Our study expanded the mutation spectrum of GARS mutations and added evidence that GARS mutations are associated with both axonal Charcot-Marie-Tooth and dHMN phenotypes. Mutations in genes encoding aminoamide tRNA synthetase (ARS) might be a frequent cause of autosomal dominant-dHMN, and SORD mutation might account for a majority of autosomal recessive-dHMN cases. The relatively low genetic diagnosis yield indicated more causative dHMN genes need to be discovered.
The COVID-19 pandemic has been causing serious disasters to mankind. The incubation period is a key parameter for epidemic control and also an important basis for epidemic prediction, but its distribution law remains unclear. This paper analyzed the epidemiological information of 787 confirmed non-Wuhan resident cases, and systematically studied the characteristics of the incubation period of COVID-19 based on the intervalcensored data estimation method. The results show that the incubation period of COVID-19 approximately conforms to the Gamma distribution with a mean value of 7.8 (95%CI:7.4-8.5) days and a median value of 7.0 (95%CI:6.7-7.3) days. The incubation period was positively correlated with age and negatively correlated with disease severity. Female cases presented a slightly higher incubation period than that of males. The proportion of infected persons who developed symptoms within 14 days was 91.6%. These results are of great significance to the prevention and control of the COVID-19 pandemic.
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