Identification of a novel mutation in the IMPDH1 gene in a Chinese family with Autosomal Dominant Retinitis Pigmentosa

Abstract

Purpose : To screen causative gene mutations in patients with RP by using Next-generation sequencing technique and to explore the function of the causative genes.

Methods : RP proband and all available family members underwent ophthalmic examination and blood samples collection.Next-generation sequencing technology was used to screen mutations.The pathogenicity of suspected mutations was analyzed using bioinformatics softwares including SIFT, PolyPhen-2 and Mutationtaster and so on to select deleterious variants. The candidate mutations were tested by Sanger sequencing.PCR-RFLP was used to identify whether the novel mutations are SNPs. Homology modeling method was used to predict the structure of the variants expressed protein.qRT-PCR was applied to evaluate the levels of the mRNA in mutation gene.

Results : We found a novel mutation c.1497G>A(p.M499I)of the known causative gene IMPDH1 which may lead to RP changes in the Chinese family. Homology modeling method showed that the variant slightly altered the structure of the protein. The IMPDH1 mRNA level in mutation type is 1.61 times higher than the level in normal type(t=-12.656,P<0.05).

Conclusions : The novel heterozygous variants c.1497G>A in IMPDH1 may be the causal mutation for RP, which has never been reported previously and needs further functional studies to prove.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

(A,B)Fundus photographs of the proband in the posterior pole showed mild degenerative changes of the retinal pigment epithelium (RPE) with an irregular visualization of the peri-vascular arch choroidal vasculature. (C,D) Fundus photographs of the proband in peripheral retina showed bone spicule-shaped pigment deposits.