Identification of novel BCL11A variants in patients with epileptic encephalopathy: Expanding the phenotypic spectrum.
Clin Genet
; 93(2): 368-373, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-28589569
ABSTRACT
BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified 2 novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p.Lys784Thr). Both the patients shared major physical features characteristic of BCL11A-related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox-Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug-resistant focal seizures and more severe developmental disability. These 2 newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease-causing variants.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encefalopatías
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Proteínas Nucleares
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Proteínas Portadoras
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Epilepsia
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Discapacidad Intelectual
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adolescent
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Child
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Female
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Humans
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Male
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Newborn
Idioma:
En
Año:
2018
Tipo del documento:
Article