Pseudodominant inheritance of autosomal recessive congenital stationary night blindness in one family with three co-segregating deleterious GRM6 variants identified by next-generation sequencing.

Hong-Yan Liu, Jia Huang, Hai Xiao, Ming-Jie Zhang, Fei-Fei Shi, Ying-Hai Jiang, Han Du, Qingzhong He, Zheng-Yuan Wang

Molecular genetics & genomic medicine 2019 Dec

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The congenital stationary night blindness (CSNB) affects the patients' dim light vision or dark adaption by impairing the normal function of retina. It is a clinically and genetically heterogeneous disorder and can be inherited in an X-linked, autosomal dominant or autosomal recessive pattern. Several genetic alterations to the genes involved in visual signal transduction of photoreceptors and/or bipolar cells underlie its pathogenesis. In this study, we used Sanger sequencing and next-generation sequencing (NGS)-based gene panel screening to investigate a family of three patients with CSNB inherited in an apparent autosomal dominant pattern. We expected to find out the disease-causing gene defects carried by this family. We found that the patients in this family did not carry the RHO, GNAT1, or PDE6B mutation, but carried compound heterozygotes mutations of GRM6. Three deleterious GRM6 variants, p.Arg621Ter, p.Gly51Val, and p.Gly464Arg, were found to be co-segregating with the disease, causing a pseudodominant inheritance of GRM6-related autosomal recessive complete CSNB. This study presents a rare case of autosomal recessive CSNB (arCSNB) pseudodominant inheritance, which potentially leads us to expand our gene candidate list in future genetic testing for apparent dominant pedigrees. The discovery of the two novel likely pathogenic variants p.Gly51Val and p.Gly464Arg could broaden our knowledge about the genetics of CSNB and provide insights into the structure and function of the GRM6 protein. © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Citation

Hong-Yan Liu, Jia Huang, Hai Xiao, Ming-Jie Zhang, Fei-Fei Shi, Ying-Hai Jiang, Han Du, Qingzhong He, Zheng-Yuan Wang. Pseudodominant inheritance of autosomal recessive congenital stationary night blindness in one family with three co-segregating deleterious GRM6 variants identified by next-generation sequencing. Molecular genetics & genomic medicine. 2019 Dec;7(12):e952