SOX10 Mutation Screening for 117 Patients with Kallmann Syndrome

Hirohito Shima, Etsuro Tokuhiro, Shingo Okamoto, Mariko Nagamori, Tsutomu Ogata, Satoshi Narumi, Akie Nakamura, Yoko Izumi, Tomoko Jinno, Erina Suzuki, Maki Fukami

研究成果: Article査読

抄録

Introduction: Kallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism (HH) and olfactory dysfunction. Although SOX10, a causative gene for Waardenburg syndrome (WS) and peripheral demyelinating neuropathy, central demyelination, WS, and Hirschsprung disease (PCWH) has previously been implicated in KS, the clinical significance of SOX10 variants as the cause of KS remains uncertain. Patients and Methods: A total of 117 patients with KS underwent mutation screening of SOX10 and 14 other causative genes for KS/HH. Rare SOX10 variants were subjected to in silico and in vitro analyses. We also examined clinical data of the patients and their parents with SOX10 variants. Results: Sequence analysis identified 2 heterozygous variants of SOX10 (c.1225G > T, p.Gly409∗ and c.475C > T, p.Arg159Trp) in patients 1-3, as well as in the parents of patients 1 and 3. The variants were assessed as pathogenic/likely pathogenic, according to the American College of Medical Genomics guidelines. Both variants lacked in vitro transactivating activity for the MITF promoter and exerted no dominant-negative effects. Patients 1-3 carried no pathogenic variants in other genes examined. The patients presented with typical KS, while such features were absent in the parents of patients 1 and 3. None of the 5 variant-positive individuals exhibited hypopigmentation, while 1 and 2 individuals exhibited complete and partial hearing loss, respectively. Conclusion: These results provide evidence that SOX10 haploinsufficiency accounts for a small percentage of KS cases. SOX10 haploinsufficiency is likely to be associated with a broad phenotypic spectrum, which includes KS without other clinical features of WS/PCWH.

本文言語English
ページ(範囲)1-7
ページ数7
ジャーナルJournal of the Endocrine Society
5
7
DOI
出版ステータスPublished - 2021 7 1
外部発表はい

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学

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