De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females.
Clin Genet
; 91(5): 756-763, 2017 05.
Article
em En
| MEDLINE
| ID: mdl-27568816
ABSTRACT
Intellectual disability (ID) affects about 3% of the population and has a male gender bias. Of at least 700 genes currently linked to ID, more than 100 have been identified on the X chromosome, including KIAA2022. KIAA2022 is located on Xq13.3 and is expressed in the developing brain. The protein product of KIAA2022, Xlinked Intellectual Disability Protein Related to Neurite Extension (XPN), is developmentally regulated and is involved in neuronal migration and cell adhesion. The clinical manifestations of lossoffunction KIAA2022 mutations have been described previously in 15 males, born from unaffected carrier mothers, but few females. Using wholeexome sequencing, we identified a cohort of five unrelated female patients with de novo probably gene damaging variants in KIAA2022 and core phenotypic features of ID, developmental delay, epilepsy refractory to treatment, and impaired language, of similar severity as reported for male counterparts. This study supports KIAA2022 as a novel cause of Xlinked dominant ID, and broadens the phenotype for KIAA2022 mutations.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epilepsia
/
Mutação com Perda de Função
/
Deficiência Intelectual
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Clin Genet
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos