Simultaneous Identification of Both MFSD8 and RDH12 Pathogenic Variants in a Chinese Family Affected With Retinitis Pigmentosa

Yihui Wang; Yanling Teng; Desheng Liang; Zhuo Li; Lingqian Wu

doi:10.3389/fgene.2021.715100

Simultaneous Identification of Both MFSD8 and RDH12 Pathogenic Variants in a Chinese Family Affected With Retinitis Pigmentosa

Front Genet. 2021 Sep 9:12:715100. doi: 10.3389/fgene.2021.715100. eCollection 2021.

Authors

Yihui Wang¹, Yanling Teng¹, Desheng Liang^{1

2}, Zhuo Li¹, Lingqian Wu^{1

2}

Affiliations

¹ Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, China.
² Hunan Jiahui Genetics Hospital, Changsha, China.

Abstract

Retinitis pigmentosa (RP) is characterized by tremendous genetic and phenotypic heterogeneity. Here, we investigate the pathogeny of RP in a family to provide evidence for genetic and reproductive counseling for families. Although this pregnant woman of 8⁺³ weeks presented with RP, her first baby was born with RP, epilepsy, and cerebellar atrophy. The research identified a compound heterozygous mutation (c.998+3_998+6del/deletion) in the MFSD8 gene of the first born, explaining the cause of the proband's disease, which cannot explain the mother's. Then, a homozygous mutation c.343+1G > A in RDH12 of the mother was found. RT-PCR is employed to find that there is a skipping of exon 10 in MFSD8 and a 15-nucleotide retention of intron5 in RDH12. The coexistence of two independent instances of RP caused by distinct genes in one pedigree is demonstrated. Based on the diagnosis, a prenatal diagnosis performed on the fetus found that the fetus's MFSD8 is affected by the same mutation as the proband. The research underscoring the complexity of RP and the need for the combination of extensive molecular genetic testing and clinical characterization in addition expands the spectrum of MFSD8 mutations. Finally, it is expected that the family members would be prevented from reproducing children with the similar disease.

Keywords: MFSD8 gene; RDH12 gene; exon skipping; intron retention; molecular testing; retinitis pigmentosa.