Beatriz Schincariol-Manhe 1, Érica Campagnolo 2, Samira Spineli-Silva 1, Nicole de Leeuw 3, Gabriela Roldão Correia-Costa 1, André Pessoa 4, Carolina Fischinger Moura de Souza 5, Cathy Stevens 6, Poupak Javaher 7, Helena Fabbri Scallet 8, Julia Mohr 9, Saskia Biskup 10, Johanna C Herkert 11, Rolph Pfundt 3, Lakshmi Mehta 12, Aisha Rekab 12, Houda Zghal Elloumi 13, May Sanyoura 13, Andréa Trevas Maciel-Guerra 1, Vera Lúcia Gil-da-Silva-Lopes 1, Ana Mondadori Dos Santos 2, Társis Paiva Vieira 14
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.
- Department of Translational Medicine – Medical Genetics and Genomic Medicine, School of Medical Sciences, Universidade Estadual de Campinas, São Paulo, Brazil.
- Universidade São Leopoldo Mandic, Campinas, São Paulo, Brazil.
- Department of Human Genetics, Radboud university medical center, Nijmegen, Netherlands.
- Hospital Infantil Albert Sabin – Fortaleza-Ce / Ceara State University – UECE, Ceará, Brazil.
- Hospital de Clinicas de Porto Alegre e Casa dos Raros, Porto Alegre, Rio Grande do Sul, Brazil.
- University of Tennessee College of Medicine, Chattanooga, TN, USA.
- Zentrum für Labormedizin, St. Gallen, Switzerland.
- Center for Molecular Biology and Genetic Engineering (CBMEG), Universidade Estadual de Campinas, Campinas, Brazil.
- Zentrum für Humangenetik Tübingen, Tübingen, Germany.
- CeGaT GmbH and Zentrum für Humangenetik Tübingen, Tübingen, Germany.
- Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
- Division of Clinical Genetics, Morgan Stanley Children’s Hospital – Columbia University Medical Center, New York, NY, USA.
- GeneDx, Gaithersburg, Maryland, USA.
- Department of Translational Medicine – Medical Genetics and Genomic Medicine, School of Medical Sciences, Universidade Estadual de Campinas, São Paulo, Brazil. tpvieira@unicamp.br.