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SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile. Genet Med 2022 Jun;24(6):1261-1273



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Scopus ID

2-s2.0-85127338633 (requires institutional sign-in at Scopus site)   10 Citations


PURPOSE: This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants.

METHODS: Individuals with protein altering variants in SOX11 were identified through exome and genome sequencing and international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation was assessed using Infinium MethylationEPIC array. The expression pattern of SOX11 in developing human brain was defined using RNAscope.

RESULTS: We reported 38 new patients with SOX11 variants. Idiopathic hypogonadotropic hypogonadism was confirmed as a feature of SOX11 syndrome. A distinctive pattern of blood DNA methylation was identified in SOX11 syndrome, separating SOX11 syndrome from other BAFopathies.

CONCLUSION: SOX11 syndrome is a distinct clinical entity with characteristic clinical features and episignature differentiating it from BAFopathies.

Author List

Al-Jawahiri R, Foroutan A, Kerkhof J, McConkey H, Levy M, Haghshenas S, Rooney K, Turner J, Shears D, Holder M, Lefroy H, Castle B, Reis LM, Semina EV, University of Washington Centre for Mendelian Genomics (UW-CMG), Lachlan K, Chandler K, Wright T, Clayton-Smith J, Hug FP, Pitteloud N, Bartoloni L, Hoffjan S, Park SM, Thankamony A, Lees M, Wakeling E, Naik S, Hanker B, Girisha KM, Agolini E, Giuseppe Z, Alban Z, Tessarech M, Keren B, Afenjar A, Zweier C, Reis A, Smol T, Tsurusaki Y, Nobuhiko O, Sekiguchi F, Tsuchida N, Matsumoto N, Kou I, Yonezawa Y, Ikegawa S, Callewaert B, Freeth M, Genomics England Research Consortium, Kleinendorst L, Donaldson A, Alders M, De Paepe A, Sadikovic B, McNeill A


Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

DNA Methylation
Klinefelter Syndrome
Neurodevelopmental Disorders
SOXC Transcription Factors