The histone demethylase family plays a key role in chromatin structure and gene regulation during development. Mutations in the genes encoding the lysine demethylase 5 (KDM5) were reported in individuals with many diseases, including neurodevelopmental disorders such as intellectual disability. Recently, KDM5B has been identified as a gene regulator causative of recessive neurodevelopmental disorders. Although numerous variants in this gene have been identified, genotype / phenotype correlation remains variable. We report a patient with two de novo mutations, a frameshift KDM5B variant and a 2q deletion of 8.2 Mb, associated with a phenotype including facial and finger dysmorphisms, severe intellectual and motor disorders, and a rare epileptic syndrome identified as epilepsy of infancy with migrating focal seizures. Comparison with previous reports suggests that the KDM5B variant could play a potential role on dysmorphic features; conversely, the epileptic disorder is mainly caused by the haploinsufficiency of the Nav1 mediated gabaergic inhibition.

Mangano GD, Antona V, Calì E, Fontana A, Salpietro V, Houlden H, et al. (2022). A complex epileptic and dysmorphic phenotype associated with a novel frameshift KDM5B variant and deletion of SCN gene cluster. SEIZURE.

A complex epileptic and dysmorphic phenotype associated with a novel frameshift KDM5B variant and deletion of SCN gene cluster

Mangano GD;Antona V;Fontana A;Nardello R
2022-04-01

Abstract

The histone demethylase family plays a key role in chromatin structure and gene regulation during development. Mutations in the genes encoding the lysine demethylase 5 (KDM5) were reported in individuals with many diseases, including neurodevelopmental disorders such as intellectual disability. Recently, KDM5B has been identified as a gene regulator causative of recessive neurodevelopmental disorders. Although numerous variants in this gene have been identified, genotype / phenotype correlation remains variable. We report a patient with two de novo mutations, a frameshift KDM5B variant and a 2q deletion of 8.2 Mb, associated with a phenotype including facial and finger dysmorphisms, severe intellectual and motor disorders, and a rare epileptic syndrome identified as epilepsy of infancy with migrating focal seizures. Comparison with previous reports suggests that the KDM5B variant could play a potential role on dysmorphic features; conversely, the epileptic disorder is mainly caused by the haploinsufficiency of the Nav1 mediated gabaergic inhibition.
apr-2022
Mangano GD, Antona V, Calì E, Fontana A, Salpietro V, Houlden H, et al. (2022). A complex epileptic and dysmorphic phenotype associated with a novel frameshift KDM5B variant and deletion of SCN gene cluster. SEIZURE.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/620402
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