Abstract
Pathogenic SOX11 variants have been associated with intellectual developmental disorder with microcephaly, and with or without ocular malformations or hypogonadotropic hypogonadism (HH) (IDDMOH, OMIM # 615866). In this article, we report seven new patients with de novo SOX11 variants. Five of the variants are missense, one nonsense, and one whole-gene deletion, most of them are novel variants. The main clinical features included neurodevelopmental delay (7/7) and intellectual disability (5/7), autism/attention deficit hyperactivity disorder (5/7), microcephaly (4/7), short stature (4/7), hypotonia (4/7), and clinodactyly of the 5th fingers (5/7). HH was confirmed in two female patients with primary amenorrhea, nonvisualized/prepubertal size of the uterus, and nonvisualized ovaries. Two of the male patients presented with micropenis, two had cryptorchidism, and one had decreased testicular size, which are suggestive findings of HH. This article contributes to the clinical characterization of patients with SOX11 variants and supports the role of this gene in HH.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank the patients and their families for their participation in this study. Also, we want to thank Annabelle Tuttle, Erin Torti, and GeneDx for their support.
Funding
This study received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – Process number 2018/08890-9); Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (Process #161749/2021-6 and #309782/2020-1), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e Fundo de Apoio ao Ensino, à Pesquisa e à Extensão (FAEPEX – Unicamp).
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BSM, AMS, and TPV designed the study, wrote, and revised the article. AMS, VLGSL, AP, CFMS, EC, JCH, PJ, CS, ATMG, LM, AR, MS, HZE, JM, and SB evaluated the patients and collected clinical data. BSM, HFS, and SSS performed the in silico analysis. BSM and GRCC performed experimental analysis. TPV, NL, and RP performed the WES analysis. All authors revised the manuscript and approved the final version of this document.
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HZE and MS are employees of GeneDx, LLC. The other authors declare no competing interests.
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Written consent for clinical data collection was given by legal guardians. Ethical approval was obtained by the respective institutional research ethics board for each individual.
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Schincariol-Manhe, B., Campagnolo, É., Spineli-Silva, S. et al. Novel variants in the SOX11 gene: clinical description of seven new patients. Eur J Hum Genet 32, 1640–1646 (2024). https://doi.org/10.1038/s41431-024-01695-8
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DOI: https://doi.org/10.1038/s41431-024-01695-8
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