EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder

Ephrin receptor and their ligands, the ephrins, are widely expressed in the developing brain. They are implicated in several developmental processes that are crucial for brain development. Deletions in genes encoding for members of the Eph/ephrin receptor family were reported in several neurodevelop...

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Published in:Clinical genetics 2021-10, Vol.100 (4), p.396-404
Main Authors: Lévy, Jonathan, Schell, Bérénice, Nasser, Hala, Rachid, Myriam, Ruaud, Lyse, Couque, Nathalie, Callier, Patrick, Faivre, Laurence, Marle, Nathalie, Engwerda, Aafke, Ravenswaaij‐Arts, Conny M. A., Plutino, Morgane, Karmous‐Benailly, Houda, Benech, Caroline, Redon, Sylvia, Boute, Odile, Boudry Labis, Elise, Rama, Mélanie, Kuentz, Paul, Assoumani, Jessica, Maldergem, Lionel Van, Dupont, Céline, Verloes, Alain, Tabet, Anne‐Claude
Format: Article
Language:English
Subjects:
6q16.1 microdeletion
Central nervous system
Chromosomes, Human, Pair 6
Comparative Genomic Hybridization
EPHA7
Ephrins
Female
Genetic Association Studies - methods
Genetic Predisposition to Disease
Haploinsufficiency
Humans
In Situ Hybridization, Fluorescence
Inheritance Patterns
intellectual disability
Life Sciences
Male
microcephaly
Mutation
neurodevelopmental disorder
Neurodevelopmental disorders
Neurodevelopmental Disorders - diagnosis
Neurodevelopmental Disorders - genetics
Patients
Pedigree
Phenotype
Phenotypes
Protein-tyrosine kinase
Receptor, EphA7 - genetics
Risk factors
speech and language development
Whole Exome Sequencing
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Summary:Ephrin receptor and their ligands, the ephrins, are widely expressed in the developing brain. They are implicated in several developmental processes that are crucial for brain development. Deletions in genes encoding for members of the Eph/ephrin receptor family were reported in several neurodevelopmental disorders. The ephrin receptor A7 gene (EPHA7) encodes a member of ephrin receptor subfamily of the protein‐tyrosine kinase family. EPHA7 plays a role in corticogenesis processes, determines brain size and shape, and is involved in development of the central nervous system. One patient only was reported so far with a de novo deletion encompassing EPHA7 in 6q16.1. We report 12 additional patients from nine unrelated pedigrees with similar deletions. The deletions were inherited in nine out of 12 patients, suggesting variable expressivity and incomplete penetrance. Four patients had tiny deletions involving only EPHA7, suggesting a critical role of EPHA7 in a neurodevelopmental disability phenotype. We provide further evidence for EPHA7 deletion as a risk factor for neurodevelopmental disorder and delineate its clinical phenotype. Mapping of the 6q16.1 deletions encompassing EPHA7 (highlighted in blue) in our patients (red bar). Four out of 12 patients have deletions encompassing only EPHA7 and share a similar phenotype, suggesting the role of EPHA7 deletion as a risk factor for neurodevelopmental disorder with developmental delay/intellectual disability, speech delay, behavioral anomalies, and/or microcephaly. The deletions were inherited in nine out of 12 patients, suggesting variable expressivity and incomplete penetrance.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.14017