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Bardet–Biedl syndrome associated with novel compound heterozygous variants in BBS12 gene

  • Clinical Case Report
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Abstract

Background

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by 6 primary features of rod-cone dystrophy, central obesity, polydactyly, cognitive impairment, hypogonadism and/or genitourinary malformations, and kidney abnormalities. At least 21 genes associated with BBS have been reported. To date, BBS associated with BBS12 variants has never been described in the Japanese population. We report a Japanese infant female with BBS with compound heterozygous BBS12 variants.

Methods

In addition to the pediatric examination, fundus photography, full-field electroretinogram(ffERG) and whole exome sequencing (WES) were underwent.

Results

The infant exhibited obesity, polydactyly, cognitive impairment, genitourinary malformations, and kidney dysfunction. At the age of 2 years, ffERG revealed severe reduction in both rod- and cone-mediated electroretinographic responses consistent with a severe form of rod-cone dystrophy, with minimal retinal abnormalities. WES revealed novel compound heterozygous BBS12 variants (c.591T > A, p.Tyr197* and c.1372dupA, p.Thr458Asnfs*5) in the infant. Her parents carried each of the variants, as confirmed by Sanger sequencing.

Conclusions

The current observations will contribute to an expanded understanding of genotype–phenotype associations in BBS12-associated BBS.

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Data availability

The data that support the findings of this report are available from the corresponding author, upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

We thank the patient and her parents for their participation in this study. We also thank Prof. Sae Ochi (Department of Laboratory Medicine, The Jikei University School of Medicine) for assistance with genetic analysis.

Funding

This work was supported, in part, by the Grants-in-Aid for Scientific Research (KAKENHI) Grant Number 21K09756 (TH) and research funds from Santen (TH; Osaka, Japan), Alcon (TH; Tokyo, Japan), Johnson and Johnson Vision, AMO (TH; Tokyo, Japan), Daiichi Sankyo (TH; Tokyo, Japan), Chugai (TH; Tokyo, Japan), Mitsubishi Tanabe Pharma (TH; Osaka, Japan), Senju (TH; Osaka, Japan), Bayer (TH; Osaka, Japan), Kyowa Kirin (TH; Tokyo, Japan), Otsuka Pharma (TH; Tokyo, Japan), Kowa (TH; Aichi, Japan), Ritz medical (TH; Aichi, Japan), Uni-hite (TH; Kanagawa, Japan), and Kuribara (TH; Gunma, Japan).

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Authors and Affiliations

  1. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan

    Tamaki Morohashi & Ichiro Morioka

  2. Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan

    Takaaki Hayashi, Kei Mizobuchi & Tadashi Nakano

  3. Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, 6-41-2 Aoto, Katsushika-Ku, Tokyo, 125-8506, Japan

    Takaaki Hayashi

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  1. Tamaki Morohashi
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Correspondence to Takaaki Hayashi.

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Conflict of interest

Takaaki Hayashi received research funds from Santen (Osaka, Japan), Alcon (Tokyo, Japan), Johnson and Johnson Vision, AMO (Tokyo, Japan), Daiichi Sankyo (Tokyo, Japan), Chugai (Tokyo, Japan), Mitsubishi Tanabe Pharma (Osaka, Japan), Senju (Osaka, Japan), Bayer (Osaka, Japan), Kyowa Kirin (Tokyo, Japan), Otsuka Pharma (Tokyo, Japan), Kowa (Aichi, Japan), Ritz medical (Aichi, Japan), Uni-hite (Kanagawa, Japan), and Kuribara (Gunma, Japan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Morohashi, T., Hayashi, T., Mizobuchi, K. et al. Bardet–Biedl syndrome associated with novel compound heterozygous variants in BBS12 gene. Doc Ophthalmol 146, 165–171 (2023). https://doi.org/10.1007/s10633-022-09915-6

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  • DOI: https://doi.org/10.1007/s10633-022-09915-6

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