Dataset Information

Identification of two novel PRPF31 mutations in Chinese families with non-syndromic autosomal dominant retinitis pigmentosa.

ABSTRACT:

Background

Retinitis pigmentosa is a heterogeneous group of inherited retinal diseases leading to progressive vision loss. It has been estimated that the etiology is still unclear in 22%-40% of cases, indicating that many novel pathogenic variations related to RP remain unidentified in many patients. In this study, our aim was to investigate the disease-causing variants and function of the variants in two Chinese families with non-syndromic autosomal dominant retinitis pigmentosa (adRP).

Methods

Clinical data and peripheral blood DNA samples were collected. Whole exome sequencing (WES) was conducted to screen for variations. Then, the expression of green fluorescent protein (GFP)-fused wild-type PRPF31 protein and its variants was evaluated via western blotting and GFP fluorescence detection in vitro.

Results

Two novel heterozygous variants of PRPF31 (NM_015629.4): c.855+5G>A and c.849_855del (p.Pro284Ilefs*35) were identified respectively in two families. The variant c.855+5G>A is co-segregated with the disease in adRP-01 family. The pedigree analysis result for c.849_855del (p. Pro284Ilefs*35) shows an inheritance pattern with incomplete penetrance for adRP-02 family. The RT-PCR analysis shows the PRPF31 gene c.855+5G>A leading to the missing from the 997th to the 1405th positions of the PRPF31 gene (NM_015629.4) cDNA. The expressions of the mutant GFP-fused PRPF31 protein were not detected in HEK293 cells or Cos7 cells via western blotting and immunofluorescence.

Conclusions

Our findings identified two novel variants in PRPF31 in two Chinese families with adRP, expanding the mutational spectrum of this gene. Functional analysis reveals that these variants lead to the truncation of the PRPF31 protein.

SUBMITTER: Cao L

PROVIDER: S-EPMC7767543 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Identification of two novel PRPF31 mutations in Chinese families with non-syndromic autosomal dominant retinitis pigmentosa.

Cao Li L Peng Chunyan C Yu Jing J Jiang Wei W Yang Jiyun J

Molecular genetics & genomic medicine 20201021 12

<h4>Background</h4>Retinitis pigmentosa is a heterogeneous group of inherited retinal diseases leading to progressive vision loss. It has been estimated that the etiology is still unclear in 22%-40% of cases, indicating that many novel pathogenic variations related to RP remain unidentified in many patients. In this study, our aim was to investigate the disease-causing variants and function of the variants in two Chinese families with non-syndromic autosomal dominant retinitis pigmentosa (adRP). ...[more]

PMID: 33085829

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Project description:Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, and 15-25% of RP is transmitted as an autosomal dominant (ad) trait. The objectives of this study were to establish the variant profile in a large cohort of adRP families and to elucidate the variant spectrum of each adRP gene in Chinese patients. A total of 138 probands clinically diagnosed with RP as a presumed autosomal dominant trait were recruited. All probands underwent ophthalmic examinations by specialists. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger DNA sequencing, and multiplex ligation probe amplification assay, was used to detect variants. We identified heterozygous variants of 11 adRP genes in 73 probands, hemizygous, or heterozygous variants of X-linked RP genes in six patients, compound heterozygous variants of autosomal recessive RP genes in three pseudodominant families, and one heterozygous variant of one ad cone and rod dystrophy gene in one proband. One proband was found carrying both variants in RPGR and FAM161A. The overall detection rate was 59.4% (82/138). We detected 72 distinct disease-causing variants involving 16 RP genes and one cone-rod dystrophy gene; 33 of these variants have not been reported previously. Disease-causing variants were identified in the adRP genes in 52.9% of the families, followed by 4.3% in the X-linked RP genes, and 2.2% in the autosomal recessive genes. The most frequent mutant genes were RHO, PRPF31, RP1, SNRNP200, and PRPF8, which explained up to 78.0% of the genetically diagnosed families. Most of the variants identified in adRP genes were missense, and copy number variations were common (7/20) in the PRPF31 gene. We established the profile of the mutated genes and the variant spectrum of adRP genes in a large cohort of Chinese patients, providing essential information for genetic counseling and future development of therapeutics for retinal dystrophy inherited as a dominant trait.

Dataset Information

Identification of two novel PRPF31 mutations in Chinese families with non-syndromic autosomal dominant retinitis pigmentosa.

Background

Methods

Results

Conclusions

Publications

Identification of two novel PRPF31 mutations in Chinese families with non-syndromic autosomal dominant retinitis pigmentosa.

Similar Datasets

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