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- Journal Article
Purpose To (i) describe a series of patients with isolated or syndromic nanophthalmos with the underlying genetic causes, including novel pathogenic variants and their functional characterization and (ii) to study the association of retinal dystrophy in patients withMFRPvariants, based on a detailed literature review of genotype-phenotype correlations. Methods Patients with nanophthalmos and available family members received a comprehensive ophthalmological examination. Genetic analysis was based on whole-exome sequencing and variant calling in core genes includingMFRP, BEST1, TMEM98, PRSS56, CRB1, GJA1, C1QTNF5, MYRFandFAM111A. A minigene assay was performed for functional characterization of a splice site variant. Results Seven patients, aged between three and 65 years, from five unrelated families were included. Novel pathogenic variants inMFRP(c.497C>T, c.899-3C>A, c.1180G>A), andPRSS56(c.1202C>A), and a recurrent de novo variant inFAM111A(c.1706G>A) in a patient with Kenny-Caffey syndrome type 2, were identified. In addition, we report co-inheritance ofMFRP-related nanophthalmos andADAR-related Aicardi-Goutieres syndrome. Conclusion Nanophthalmos is a genetically heterogeneous condition, and the severity of ocular manifestations appears not to correlate with variants in a specific gene. However, retinal dystrophy is only observed in patients harbouring pathogenicMFRPvariants. Furthermore, heterozygous carriers ofMFRPandPRSS56should be screened for the presence of high hyperopia. Identifying nanophthalmos as an isolated condition or as part of a syndrome has implications for counselling and can accelerate the interdisciplinary care of patients. Show more
Journal / seriesActa ophthalmologica
SubjectFAM111A; Kenny-Caffey syndrome; MFRP; nanophthalmia; nanophthalmos; posterior microphthalmos; PRSS56
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