Identification of novel BCL11A variants in patients with epileptic encephalopathy: Expanding the phenotypic spectrum.

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.

• Authors: M Yoshida, M Nakashima, T Okanishi, S Kanai, A Fujimoto, K Itomi, M Morimoto, H Saitsu, M Kato, N Matsumoto, T Chiyonobu
• Journal: Clinical genetics (Clin Genet) Vol. 93 Issue 2 Pg. 368-373 (Feb 2018) ISSN: 1399-0004 [Electronic] Denmark
• PMID: 28589569 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• BCL11A protein, human
• Carrier Proteins
• Nuclear Proteins
• Repressor Proteins

Topics

• Adolescent
• Brain Diseases (genetics, physiopathology)
• Carrier Proteins (genetics)
• Child
• Epilepsy (genetics, physiopathology)
• Female
• Frameshift Mutation (genetics)
• Humans
• Infant, Newborn
• Intellectual Disability (genetics, physiopathology)
• Lennox Gastaut Syndrome (genetics, physiopathology)
• Male
• Nuclear Proteins (genetics)
• Repressor Proteins
• Spasms, Infantile (genetics, physiopathology)
• Exome Sequencing