ERBB4 exonic deletions on chromosome 2q34 in patients with intellectual disability or epilepsy.

Autor: Hyder Z; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK. zerin.hyder@mft.nhs.uk., Van Paesschen W; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.; Laboratory for Epilepsy Research, Katholieke Universiteit Leuven, Leuven, Belgium., Sabir A; West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK., Sansbury FH; All Wales Medical Genomics Service, NHS Wales Cardiff and Vale University Health Board, Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK., Burke KB; All Wales Medical Genomics Service, NHS Wales Cardiff and Vale University Health Board, Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK., Khan N; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Chandler KE; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.; Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Cooper NS; West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK., Wright R; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., McHale E; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Van Esch H; Center for Human Genetics, University Hospitals Leuven, University of Leuven, Leuven, Belgium., Banka S; Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.; Division of Evolution & Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2021 Sep; Vol. 29 (9), pp. 1377-1383. Date of Electronic Publication: 2021 Feb 18.
DOI: 10.1038/s41431-021-00815-y
Abstrakt: ERBB4 encodes the tyrosine kinase receptor HER4, a critical regulator of normal cell function and neurodevelopmental processes in the brain. One of the key ligands of HER4 is neureglin-1 (NRG1), and the HER4-NRG1 signalling pathway is essential in neural crest cell migration, and neuronal differentiation. Pharmacological inactivation of HER4 has been shown to hasten the progression of epileptogenesis in rodent models, and heterozygous ERBB4 null mice are shown to have cognitive deficits and delayed motor development. Thus far there is only a single case report in the literature of a heterozygous ERBB4 deletion in a patient with intellectual disability (ID). We identified nine subjects from five unrelated families with chromosome 2q34 deletions, resulting in heterozygous intragenic loss of multiple exons of ERBB4, associated with either non-syndromic ID or generalised epilepsy. In one family, the deletion segregated with ID in five affected relatives. Overall, this case series further supports that haploinsufficiency of ERBB4 leads to non-syndromic intellectual disability or epilepsy.
(© 2021. Crown.)
Databáze: MEDLINE
Externí odkaz: