1. Главная
  2. Ресурсы
  3. Библиотечный поиск
BCL11AHaploinsufficiencyCauses anIntellectualDisability Syndromeand DysregulatesTranscription Cristina DiasSara B. EstruchSarah A. Graham2016 год

BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.
Год издания: 2016
Авторы: Cristina Dias, Sara B. Estruch, Sarah A. Graham, Jeremy F. McRae, Stephen J. Sawiak, Jane A. Hurst, Shelagh Joss, Susan Holder, Jenny E.V. Morton, Claire Turner, Julien Thévenon, Kelly Mellul, Gabriela Sánchez-Andrade, Ximena Ibarra-Soria, Pelagia Derizioti, Rui F. Santos, Song‐Choon Lee, Laurence Faivre, Tjitske Kleefstra, Pentao Liu, M.E. Hurles, Simon E. Fisher, Darren W. Logan
Издательство: Elsevier BV
Источник: The American Journal of Human Genetics
Ключевые слова: Chromatin Remodeling and Cancer, Genomic variations and chromosomal abnormalities, Genomics and Chromatin Dynamics
Другие ссылки: The American Journal of Human Genetics (HTML)
HAL (Le Centre pour la Communication Scientifique Directe) (HTML)
ube.hal.science (HTML)
HAL (Le Centre pour la Communication Scientifique Directe) (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
MPG.PuRe (Max Planck Society) (PDF)
MPG.PuRe (Max Planck Society) (HTML)
Radboud Repository (Radboud University) (HTML)
Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (PDF)
Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (HTML)
Research Portal (King's College London) (PDF)
Research Portal (King's College London) (HTML)
Research Portal (King's College London) (HTML)
Data Archiving and Networked Services (DANS) (PDF)
Data Archiving and Networked Services (DANS) (HTML)
PubMed Central (HTML)
PubMed (HTML)