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Bardet–Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations

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Abstract

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by retinitis pigmentosa (RP), truncal obesity, cognitive impairment, hypogonadism in men, polydactyly, and renal abnormalities with severe renal dysfunction. Twenty-two causative genes have already been reported for this disorder. In this study, we identified two unrelated Japanese patients with clinical diagnoses of BBS associated with compound heterozygous SCLT1 mutation. Patient 1 was a 10-year-old girl, and patient 2 was a 22-year-old man. Both the patients showed severe renal dysfunction in childhood, RP, mild intellectual disability, short stature, and truncal obesity, without oral aberrations and polydactyly. Patient 2 also had hypogonadism. We identified two missense variants in SCLT1, c.[1218G > A] and [1631A > G], in both the patients by next-generation sequencing. Subsequent cDNA analysis revealed that c.1218G > A affected exon 14 skipping in SCLT1. To date, SCLT1 has been reported as the causative gene of oral–facial–digital syndrome type IX, and Senior–Løken syndrome. The phenotypes of both the present patients were compatible with BBS. These results highlight SCLT1 as an additional candidate for BBS phenotype in an autosomal recessive manner.

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Acknowledgements

The authors thank all the study participants and their families. We are profoundly grateful to Mrs. Yoshimi Nozu (Kobe University) for her excellent technical assistance. We would like to thank Editage (www.editage.jp) for English language editing. This work was supported by the Health Labor Sciences Research Grant for the Research on Measures for Intractable Diseases (H24-nanchi-ippan-041 to K.I.; H29-nanchi-ippan-039 to N.M.), and the Japan Society for the Promotion of Science (KAKENHI Grant number JP15K09261 and 18K08243 to N.M.).

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Correspondence to Naoya Morisada.

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Kazumoto Iijima received funding support from Daiichi Sankyo Co., Ltd., Zenyaku Kogyo Co., Ltd. and Astellas Pharma, Inc.

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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 at which the studies were conducted (IRB approval number 86 and 301) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Morisada, N., Hamada, R., Miura, K. et al. Bardet–Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations. CEN Case Rep 9, 260–265 (2020). https://doi.org/10.1007/s13730-020-00472-y

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