Novel variants in the SOX11 gene: clinical description of seven new patients

• Published in: European journal of human genetics : EJHG 2024-12, Vol.32 (12), p.1640-1646
• Main Authors: Schincariol-Manhe, Beatriz, Campagnolo, Érica, Spineli-Silva, Samira, de Leeuw, Nicole, Correia-Costa, Gabriela Roldão, Pessoa, André, de Souza, Carolina Fischinger Moura, Stevens, Cathy, Javaher, Poupak, Scallet, Helena Fabbri, Mohr, Julia, Biskup, Saskia, Herkert, Johanna C., Pfundt, Rolph, Mehta, Lakshmi, Rekab, Aisha, Elloumi, Houda Zghal, Sanyoura, May, Maciel-Guerra, Andréa Trevas, Gil-da-Silva-Lopes, Vera Lúcia, dos Santos, Ana Mondadori, Vieira, Társis Paiva
• Format: Article
• Language: English
• Subjects: 45/23; 45/61; 631/208/1516/1510; 692/308; Adolescent; Adult; Amenorrhea; Attention deficit hyperactivity disorder; Autism; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Brief Communication; Child; Child, Preschool; Collaboration; Cryptorchidism; Cytogenetics; Female; Gene deletion; Gene Expression; Genes; Genetic engineering; Genetic testing; Human Genetics; Humans; Hypogonadism; Hypogonadism - genetics; Hypogonadism - pathology; Intellectual disabilities; Intellectual Disability - genetics; Intellectual Disability - pathology; Laboratories; Male; Microcephaly; Microcephaly - genetics; Microcephaly - pathology; Microencephaly; Mutation; Mutation, Missense; Neurodevelopmental disorders; Ovaries; Patients; Phenotype; Proteins; SOXC Transcription Factors - genetics; Transcription factors; Uterus
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/s41431-024-01695-8

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.