MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype.
Neurogenetics
; 19(2): 93-103, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29511999
ABSTRACT
Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complexo Mediador
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Deficiência Intelectual
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article