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Identification of novel BCL11A variants in patients with epileptic encephalopathy: Expanding the phenotypic spectrum
Author(s) -
Yoshida M.,
Nakashima M.,
Okanishi T.,
Kanai S.,
Fujimoto A.,
Itomi K.,
Morimoto M.,
Saitsu H.,
Kato M.,
Matsumoto N.,
Chiyonobu T.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13067
Subject(s) - haploinsufficiency , frameshift mutation , intellectual disability , epilepsy , phenotype , exome sequencing , genetics , fetal hemoglobin , global developmental delay , medicine , status epilepticus , biology , neuroscience , fetus , gene , pregnancy
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.