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

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

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.