Maternal Uniparental Isodisomy of Chromosome 4 and 8 in Patients with Retinal Dystrophy: SRD5A3-Congenital Disorders of Glycosylation and RP1-Related Retinitis Pigmentosa.

Nobutaka Tachibana,Yoshihiro Hotta,Hirotomo Saitsu,Nobuhiko Okamoto,Sachiko Nishina,Kaoruko Torii,Tsutomu Ogata,Shuichi Shimakawa,Shuhei Nomura,Miho Sato,Shinji Arai,Kentaro Kurata,Yoshinao Wada,Katsuhiro Hosono,Noriyuki Azuma

doi:10.3390/genes13020359

Abstract

Purpose: Uniparental disomy (UPD) is a rare chromosomal abnormality. We performed whole-exosome sequencing (WES) in cases of early-onset retinal dystrophy and identified two cases likely caused by UPD. Herein, we report these two cases and attempt to clarify the clinical picture of retinal dystrophies caused by UPD. Methods: WES analysis was performed for two patients and their parents, who were not consanguineous. Functional analysis was performed in cases suspected of congenital disorders of glycosylation (CDG). We obtained clinical case data and reviewed the literature. Results: In case 1, a novel c.57G>C, p.(Trp19Cys) variant in SRD5A3 was detected homozygously. Genetic analysis suggested a maternal UPD on chromosome 4, and functional analysis confirmed CDG. Clinical findings showed early-onset retinal dystrophy, intellectual disability, and epilepsy. In case 2, an Alu insertion (c.4052_4053ins328, p.[Tyr1352Alafs]) in RP1 was detected homozygously. Maternal UPD on chromosome 8 was suspected. The clinical picture was consistent with RP1-related retinitis pigmentosa. Although the clinical features of retinal dystrophy by UPD may vary, most cases present with childhood onset. Conclusions: There have been limited reports of retinal dystrophy caused by UPD, suggesting that it is rare. Genetic counseling may be encouraged in pediatric cases of retinal dystrophy.

Highlights

Uniparental disomy (UPD) is a rare event in which an individual with a diploid genome carries either two homologs of a pair of chromosomes from one parent or two copies of a single chromosome from one parent [1,4]
We report two cases of retinal dystrophy caused by UPD
Each case was diagnosed as SRD5A3-congenital disorders of glycosylation (CDG) and RP1-related retinitis pigmentosa (RP), and the clinical picture was equivalent to that without UPD

Summary

Introduction

Uniparental disomy (UPD) is a rare event in which an individual with a diploid genome carries either two homologs of a pair of chromosomes from one parent (uniparental heterodisomy), or two copies of a single chromosome from one parent (uniparental isodisomy) [1]. It is divided into paternal and maternal UPD, depending on whether the homologous chromosomes are derived from the father or mother, respectively [2]. We present two cases of early-onset retinal dystrophy, including congenital disorders of glycosylation (CDG), caused by maternal UPD, examined via whole-exome sequencing (WES). We report detailed clinical features of the two cases and review previous reports of retinal dystrophy cases with UPD, obtained via a search of PubMed, to characterize their clinical features

Methods

Results

Conclusion