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Zhen Yii, Qingjiong Zhang; Biallelic Mutations in a Novel Gene FAM*** are Associated with Inherited Retinal Dystrophies. Invest. Ophthalmol. Vis. Sci. 2019;60(9):380.
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© ARVO (1962-2015); The Authors (2016-present)
Inherited retinal dystrophies (IRDs) are the major causes of irreversible blindness in children, adolescent, and working-age people. In this study, the objective was to identify pathogenic variants in two unsolved Chinese families with IRDs.
To identify the genetic defect, whole-exome sequencing (WES) and clinical analysis was performed in both probands with IRDs, as well as in 1974 in-house controls with other hereditary eye diseases. The expression profiles, as well as the phenotype analysis of knockout mice model, were performed to investigate the function of FAM*** in photoreceptors.
By analysing WES data based on allele frequencies of in-house controls, population allele frequencies, and in silico prediction tools, two rare compound heterozygeous mutations in FAM*** were identified in two unrelated families. Quantitative real-time PCR revealed the expression of FAM*** in human retina and its progressively increased expression during postnatal retinal development in mice. Immunohistochemistry of FAM*** in the human retinal sections revealed enriched expression in the outer segments of rod photoreceptors. There was no significant retinal degeneration in FAM*** gene knockout mice in 15 weeks.
Our study implicates that biallelic mutations in FAM*** are associated with the occurrence of IRDs. Moreover, the specific expression in photoreceptors indicates that FAM*** may play an important role in the maintenance of photoreceptor function. The lack of retinal degeneration phenotypes in FAM*** gene knockout mice may owe to their relatively younger age.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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