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01-08-2020 | Clinical Case Report

Novel biallelic splice-site BBS1 variants in Bardet–Biedle syndrome: a case report of the first Japanese patient

Authors: Satoshi Katagiri, Katsuhiro Hosono, Takaaki Hayashi, Noriyuki Murai, Eiichi Wake, Ichiro Miyata, Kei Mizobuchi, Kentaro Kurata, Tomokazu Matsuura, Tadashi Nakano, Yoshihiro Hotta

Published in: Documenta Ophthalmologica | Issue 1/2020

Abstract

Purpose

To report the clinical and genetic features of a 9-year-old female Japanese patient with Bardet–Biedl syndrome (BBS).

Methods

Genetic analysis using whole-exome sequencing (WES) was performed for the patient and her parents to identify disease-causing variants. Reverse transcriptase–polymerase chain reaction (RT–PCR) was performed to investigate the impact of splice-site variants. Comprehensive ophthalmic and systemic examinations, including electroretinography (ERG), were performed.

Results

In the patient, WES identified novel compound heterozygous splice-site variants (c.124+2T>G and c.723+2T>G) in the BBS1 gene, and RT–PCR revealed skipping of exons 2 and 8 (p.N17AfsX56 and p.T198_K241del). Each parent had one of the variants. Ophthalmologically, the patient’s decimal best-corrected visual acuity was 0.6 in the right eye and 0.4 in the left eye. Funduscopy revealed no apparent retinal degeneration or narrowed blood vessels in the periphery, but macular abnormalities were found on fundus autofluorescence imaging and optical coherence tomography images. Unexpectedly, non-recordable responses in rod ERG were found, with a non-recordable response of the right eye and an extremely reduced and delayed a-wave of the left eye in standard ERG, non-recordable responses in cone ERG, and extremely decreased responses in 30 Hz flicker ERG. Finally, the patient fulfilled four primary features of BBS diagnostic criteria: rod-cone dystrophy, polydactyly, central obesity, and learning disabilities, being diagnosed with BBS.

Conclusions

This is the first report of a BBS patient with biallelic splice-site BBS1 variants in the Japanese population. Disparity between funduscopic and ERG findings may be a feature of BBS1-associated rod-cone dystrophy.

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Title: Novel biallelic splice-site BBS1 variants in Bardet–Biedle syndrome: a case report of the first Japanese patient
Authors: Satoshi Katagiri
Katsuhiro Hosono
Takaaki Hayashi
Noriyuki Murai
Eiichi Wake
Ichiro Miyata
Kei Mizobuchi
Kentaro Kurata
Tomokazu Matsuura
Tadashi Nakano
Yoshihiro Hotta
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Published in: Documenta Ophthalmologica / Issue 1/2020
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI: https://doi.org/10.1007/s10633-020-09752-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Novel biallelic splice-site BBS1 variants in Bardet–Biedle syndrome: a case report of the first Japanese patient

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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