SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

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, L.M.; Semina, E.V.; Lachlan, K.; Chandler, K.; Wright, T.; Clayton-Smith, J.; Hug, F.P.; Pitteloud, N.; Bartoloni, L.; Hoffjan, S.; Park, S.M.; Thankamony, A.; Lees, M.; Wakeling, E.; Naik, S.; Hanker, B.; Girisha, K.M.; 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.; Kleinendorst, L.; Donaldson, A.; Alders, M.; De Paepe, A.; Sadikovic, B.; McNeill, A.

doi:10.1016/j.gim.2022.02.013

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

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Serval ID

serval:BIB_FD0B4538B921

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

Journal

Genetics in medicine

Author(s)

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 L.M., Semina E.V., Lachlan K., Chandler K., Wright T., Clayton-Smith J., Hug F.P., Pitteloud N., Bartoloni L., Hoffjan S., Park S.M., Thankamony A., Lees M., Wakeling E., Naik S., Hanker B., Girisha K.M., 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., Kleinendorst L., Donaldson A., Alders M., De Paepe A., Sadikovic B., McNeill A.

Working group(s)

University of Washington Centre for Mendelian Genomics (UW-CMG), Genomics England Research Consortium

Contributor(s)

Nickerson D., Bamshad M., Leal S., Ambrose J.C., Arumugam P., Bevers R., Bleda M., Boardman-Pretty F., Boustred C.R., Brittain H., Caulfield M.J., Chan G.C., Elgar G., Fowler T., Giess A., Hamblin A., Henderson S., Hubbard TJP, Jackson R., Jones L.J., Kasperaviciute D., Kayikci M., Kousathanas A., Lahnstein L., Leigh SEA, Leong IUS, Lopez J.F., Maleady-Crowe F., McEntagart M., Minneci F., Moutsianas L., Mueller M., Murugaesu N., Need A.C., O'Donovan P., Odhams C.A., Patch C., Pereira M.B., Perez-Gil D., Pullinger J., Rahim T., Rendon A., Rogers T, Savage K., Sawant K., Scott R.H., Siddiq A., Sieghart A., Smith S.C., Sosinsky A., Stuckey A., Tanguy M., Taylor Tavares A.L., Thomas ERA, Thompson S.R., Tucci A., Welland M.J., Williams E., Witkowska K., Wood S.M.

ISSN

1530-0366 (Electronic)

ISSN-L

1098-3600

Publication state

Published

Issued date

06/2022

Peer-reviewed

Oui

Volume

Number

Pages

1261-1273

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Abstract

This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants.
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.
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.
SOX11 syndrome is a distinct clinical entity with characteristic clinical features and episignature differentiating it from BAFopathies.

Keywords

DNA Methylation/genetics, Humans, Hypogonadism/genetics, Klinefelter Syndrome/genetics, Neurodevelopmental Disorders/genetics, Phenotype, SOXC Transcription Factors/genetics, Exome Sequencing, Exome, Genome sequencing, Hypogonadism, Methylation, Neurodevelopmental disorder, SOX11

OAI-PMH

oai:serval.unil.ch:BIB_FD0B4538B921

DOI

10.1016/j.gim.2022.02.013

Pubmed

35341651

Web of science

000806512700010

Open Access

Yes

Create date

09/04/2022 19:36