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.
A complex epileptic and dysmorphic phenotype associated with a novel frameshift KDM5B variant and deletion of SCN gene cluster / G.D. Mangano, V. Antona, E. Cali, A. Fontana, V. Salpietro, H. Houlden, P. Veggiotti, R. Nardello. - In: SEIZURE. - ISSN 1059-1311. - 97:(2022 Apr), pp. 20-22. [10.1016/j.seizure.2022.03.001]
A complex epileptic and dysmorphic phenotype associated with a novel frameshift KDM5B variant and deletion of SCN gene cluster
P. VeggiottiPenultimo
;
2022
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.File | Dimensione | Formato | |
---|---|---|---|
A complex epileptic and dysmorphic phenotype associated with a novel frameshift KDM5B variant and deletion of SCN gene cluster.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
6.32 MB
Formato
Adobe PDF
|
6.32 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.