Loss-of-function variants in ZEB1 cause dominant anomalies of the corpus callosum with favourable cognitive prognosis

被引：0

作者：

Heide, Solveig ^{[1
,2
,20
]}

Argilli, Emanuela ^{[3
,4
,5
]}

Valence, Stephanie ^{[6
,7
]}

Boutaud, Lucile ^{[8
]}

Roux, Nathalie ^{[8
]}

Mignot, Cyril ^{[1
,2
]}

Nava, Caroline ^{[9
]}

Keren, Boris ^{[9
]}

Giraudat, Kim ^{[6
,7
]}

Faudet, Anne ^{[1
,2
]}

Gerasimenko, Anna ^{[1
,2
]}

Garel, Catherine ^{[10
]}

Blondiaux, Eleonore ^{[10
]}

Rastetter, Agnes ^{[11
]}

Grevent, David ^{[12
,13
,14
]}

Le, Carolyn ^{[4
,5
,15
,16
]}

Mackenzie, Lisa ^{[17
]}

Richards, Linda ^{[17
,18
]}

Attie-Bitach, Tania ^{[8
]}

Depienne, Christel ^{[19
]}

Sherr, Elliott ^{[3
,4
,5
]}

Heron, Delphine ^{[1
,2
]}

机构：

[1] Sorbonne Univ, Pitie Salpetriere Hosp, Assistance Publ Hop Paris, Dept Genet, F-75013 Paris, France

[2] Sorbonne Univ, Pitie Salpetriere Hosp, Assistance Publ Hop Paris, AP HP,Referral Ctr Intellectual Disabil Rare Caus, F-75013 Paris, France

[3] Univ Calif San Francisco, Dept Neurol, Div Hosp Med, San Francisco, CA USA

[4] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA USA

[5] Univ Calif San Francisco, Weill Inst Neurosci, San Francisco, CA USA

[6] Sorbonne Univ, Hop Armand Trousseau, Dept Neuropediatry, Paris, France

[7] Sorbonne Univ, Hop Armand Trousseau, AP HP, Referral Ctr Intellectual Disabil Rare Causes, Paris, France

[8] Hop Univ Necker Enfants Malad, Assistance Publ Hop Paris, Genom Med Rare Dis, UF MP5, Paris, France

[9] Sorbonne Univ, Pitie Salpetriere Hosp, Dept Genet, Unit Dev Genom,AP HP, Paris, France

[10] Sorbonne Univ, Armand Trousseau Hosp, Assistance Publ Hop Paris AP HP, Dept Pediat & Prenatal Imaging, Paris, France

[11] Sorbonne Univ, Paris Brain Inst, ICM Inst Cerveau, INSERM,UMR S 1127, Paris, France

[12] Hop Univ Necker Enfants Malad, Radiol Dept, Paris, France

[13] Univ Paris, EA Fetus 7328, Paris, France

[14] Univ Paris, LUMIERE Platform, Paris, France

[15] Univ Calif San Francisco, Inst Human Genet, Dept Neurol, San Francisco, CA USA

[16] Weill Inst Neurosci, San Francisco, CA USA

[17] Washington Univ St Louis, Sch Med, Dept Neurosci, St Louis, MO USA

[18] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[19] Univ Duisburg Essen, Univ Hosp Essen, Inst Human Genet, Essen, Germany

[20] Sorbonne Univ, Pitie Salpetriere Hosp, Assistance Publ Hop Paris, Dept Genet, Paris, France

来源：

JOURNAL OF MEDICAL GENETICS | 2024年 / 61卷 / 03期

关键词：

Genetics; Medical; Neurology; Nervous System Malformations; POLYMORPHOUS CORNEAL-DYSTROPHY; AGENESIS; GENE; MIGRATION; DELETIONS; SPECTRUM;

D O I：

10.1136/jmg-2023-109293

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background The neurodevelopmental prognosis of anomalies of the corpus callosum (ACC), one of the most frequent brain malformations, varies extremely, ranging from normal development to profound intellectual disability (ID). Numerous genes are known to cause syndromic ACC with ID, whereas the genetics of ACC without ID remains poorly deciphered.Methods Through a collaborative work, we describe here ZEB1, a gene previously involved in an ophthalmological condition called type 3 posterior polymorphous corneal dystrophy, as a new dominant gene of ACC. We report a series of nine individuals with ACC (including three fetuses terminated due to ACC) carrying a ZEB1 heterozygous loss-of-function (LoF) variant, identified by exome sequencing.Results In five cases, the variant was inherited from a parent with a normal corpus callosum, which illustrates the incomplete penetrance of ACC in individuals with an LoF in ZEB1. All patients reported normal schooling and none of them had ID. Neuropsychological assessment in six patients showed either normal functioning or heterogeneous cognition. Moreover, two patients had a bicornuate uterus, three had a cardiovascular anomaly and four had macrocephaly at birth, which suggests a larger spectrum of malformations related to ZEB1.Conclusion This study shows ZEB1 LoF variants cause dominantly inherited ACC without ID and extends the extraocular phenotype related to this gene.

引用

页码：244 / 249

页数：6

共 26 条

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