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Bardet–Biedl syndrome and related disorders in Japan

Journal of Human Genetics volume 65, pages 847–853 (2020)Cite this article

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Abstract

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by obesity, mental impairment, rod-cone dystrophy, polydactyly, male hypogonadism, and renal abnormalities. This disorder is caused by mutations in BBS1-21. Alström syndrome (AS), caused solely by mutations in ALMS1, is another genetic obesity syndrome clinically similar to BBS. We previously conducted the first nationwide survey of BBS in Japan and found four patients with genetically definite BBS. In this study, exome analyses were performed on new patients whose symptoms fulfilled the diagnostic criteria for BBS. We identified one reported heterozygous mutation in BBS1 (p.R429*) in one patient, two novel mutations (p.L493R and p.H719Y) in BBS20 in a second patient, and one novel mutation (p.Q920*) and one reported mutation (p.R2928*) in ALMS1 in a third patient, who was subsequently diagnosed with AS. The first patient with BBS was previously considered to have digenic heterozygous mutations in BBS1 and BBS4. RT-PCR and long-range genomic PCR analyses identified a new heterozygous mutation in BBS1, the deletion of exons 10 and 11. Thus, this patient was compound heterozygous for mutations in BBS1. Many studies have described digenic heterozygous mutations in BBS. However, undetected mutations might have existed in either one of the mutated genes.

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Author notes

  1. These authors contributed equally: Makito Hirano, Wataru Satake

Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Kindai University, Osakasayama, Japan

    Makito Hirano & Susumu Kusunoki

  2. Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan

    Wataru Satake & Pei-Chieng Cha

  3. Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Wataru Satake & Tatsushi Toda

  4. Department of Pediatrics, Hitachinaka Hospital, Hitachi, Japan

    Nobuko Moriyama

  5. Department of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan

    Ken Saida

  6. Department of Medical Genetics, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Nobuhiko Okamoto

  7. Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan

    Yutaka Suzuki

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  1. Makito Hirano
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  2. Wataru Satake
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  4. Ken Saida
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  7. Yutaka Suzuki
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  8. Susumu Kusunoki
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  9. Tatsushi Toda
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Contributions

Design or conceptualization of the study: MH, WS, and TT. Analysis or interpretation of the data: MH, WS, NM, KS, YS, and PCC. Drafting or revising the manuscript for intellectual content: MH, WS, SK, and TT.

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Correspondence to Makito Hirano.

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Hirano, M., Satake, W., Moriyama, N. et al. Bardet–Biedl syndrome and related disorders in Japan. J Hum Genet 65, 847–853 (2020). https://doi.org/10.1038/s10038-020-0778-y

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