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

Abstract

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.

Metadata

Authors/Creators:

Al-Jawahiri, R https://orcid.org/0000-0002-5689-3368
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
Lachlan, K
Chandler, K
Wright, T
Clayton-Smith, J
Hug, FP
Pitteloud, N
Bartoloni, L
Hoffjan, S
Park, S-M
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 https://orcid.org/0000-0003-0534-9095
Kleinendorst, L
Donaldson, A
Alders, M
De Paepe, A
Sadikovic, B
McNeill, A
Nickerson, D
Bamshad, M
Leal, S
Ambrose, JC
Arumugam, P
Bevers, R
Bleda, M
Boardman-Pretty, F
Boustred, CR
Brittain, H
Caulfield, MJ
Chan, GC
Elgar, G
Fowler, T
Giess, A
Hamblin, A
Henderson, S
Hubbard, TJP
Jackson, R
Jones, LJ
Kasperaviciute, D
Kayikci, M
Kousathanas, A
Lahnstein, L
Leigh, SEA
Leong, IUS
Lopez, JF
FionaMaleady-Crowe
McEntagart, M
Minneci, F
Moutsianas, L
Mueller, M
Murugaesu, N
Need, AC
O’Donovan, P
Odhams, CA
Patch, C
Pereira, MB
Perez-Gil, D
Pullinger, J
TahrimaRahim
Rendon, A
TimRogers
Savage, K
Sawant, K
Scott, RH
Siddiq, A
Sieghart, A
Smith, SC
Sosinsky, A
Stuckey, A
Tanguy, M
Taylor Tavares, AL
Thomas, ERA
Thompson, SR
Tucci, A
Welland, MJ
Williams, E
Witkowska, K
Wood, SM

© 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Keywords:

Exome; Genome sequencing; Hypogonadism; Methylation; Neurodevelopmental disorder; SOX11

Dates: