Novel compound heterozygous mutations in the CHST6 gene cause macular corneal dystrophy in a Han Chinese family

Yanxia Huang; Lamei Yuan; Yanna Cao; Renhong Tang; Hongbo Xu; Ziqian Tang; Hao Deng

doi:10.21037/atm-20-7178

Novel compound heterozygous mutations in the CHST6 gene cause macular corneal dystrophy in a Han Chinese family

Ann Transl Med. 2021 Apr;9(8):622. doi: 10.21037/atm-20-7178.

Authors

Yanxia Huang¹, Lamei Yuan¹, Yanna Cao², Renhong Tang², Hongbo Xu¹, Ziqian Tang¹, Hao Deng^{1

3

4}

Affiliations

¹ Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
² Department of Ophthalmology, the Third Xiangya Hospital, Central South University, Changsha, China.
³ Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
⁴ Disease Genome Research Center, Central South University, Changsha, China.

Abstract

Background: Macular corneal dystrophy (MCD), a rare autosomal recessive disorder, is caused by pathogenic mutations in the carbohydrate sulfotransferase 6 gene (CHST6) and is characterized by bilateral progressive stromal clouding and vision loss. Corneal transplantation is often necessary. This study aimed to identify disease-causing mutations in a Han-Chinese MCD patient.

Methods: A 37-year-old female diagnosed with MCD was recruited. The clinical materials were observed and described, and peripheral blood sample was extracted. Whole exome sequencing (WES) and Sanger sequencing were used to reveal genetic defects. The pathogenicity of identified mutations was assessed using in silico analysis.

Results: The patient had typical features of MCD, including decreased vision, multiple irregular gray-white corneal opacities, and corneal thinning. A novel nonsense mutation c.544C>T (p.Gln182Ter) and a validated missense mutation c.631C>G (p.Arg211Gly) were identified in the CHST6 gene coding region, both classified as "pathogenic" following the American College of Medical Genetics and Genomics standards and guidelines.

Conclusions: This study reports a Han-Chinese MCD patient with a novel nonsense mutation c.544C>T (p.Gln182Ter) and a recurrent missense mutation c.631C>G (p.Arg211Gly), which expand the spectrum of genetic mutations. The results of this study extend genotype-phenotype correlations between the CHST6 gene mutations and MCD clinical findings, contributing to a more accurate diagnosis and the development of potential gene-targeted MCD therapies.

Keywords: Carbohydrate sulfotransferase 6 gene (CHST6); compound heterozygous mutations; Han Chinese family; macular corneal dystrophy (MCD).