AUTHOR=Jin Jie-Yuan , Wu Pan-Feng , He Ji-Qiang , Fan Liang-Liang , Yuan Zhuang-Zhuang , Pang Xiao-Yang , Tang Ju-Yu , Zhang Li-Yang 

TITLE=Novel Compound Heterozygous DST Variants Causing Hereditary Sensory and Autonomic Neuropathies VI in Twins of a Chinese Family

JOURNAL=Frontiers in Genetics

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00492

DOI=10.3389/fgene.2020.00492

ISSN=1664-8021

ABSTRACT=Background: Hereditary sensory and autonomic neuropathies (HSAN) are a rare and severe group of sensory axonal neuropathies. HSAN have been classified into eight groups based on inheritance, clinical features and the related genes. And HSAN-VI perhaps is the most notable one. HSAN-VI is an autosomal recessive disease, which manifests the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and even early death. Genetic researches indicate that DST is a causative gene. DST encodes dystonin, a member of the plakin proteins family that is involved in cytoskeletal filament networks. Dystonin has seven major neuronal isoforms in nerve, muscle and epithelium.
Material and Methods: The present study investigated a Chinese family with HSAN, and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of pathogenic of the variants. Co-segregation were subsequently conducted.
Results: We identified the compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients.
Conclusion: We reported a Chinese HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.