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Dissection of contiguous gene effects for deletions around ERF on chromosome 19
Author(s) -
Calpena Eduardo,
McGowan Simon J.,
Blanco Kelly Fiona,
BoudryLabis Elise,
DieuxCoeslier Anne,
Harrison Rachel,
Johnson Diana,
Lachlan Katherine,
Morton Jenny E. V.,
Stewart Helen,
Vasudevan Pradeep,
Twigg Stephen R. F.,
Wilkie Andrew O. M.
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24213
Subject(s) - biology , genetics , gene , haploinsufficiency , loss function , copy number variation , exon , craniosynostosis , deletion mapping , genome , chromosome , subtelomere , phenotype
Heterozygous intragenic loss‐of‐function mutations of ERF , encoding an ETS transcription factor, were previously reported to cause a novel craniosynostosis syndrome, suggesting that ERF is haploinsufficient. We describe six families harboring heterozygous deletions including, or near to, ERF , of which four were characterized by whole‐genome sequencing and two by chromosomal microarray. Based on the severity of associated intellectual disability (ID), we identify three categories of ERF ‐associated deletions. The smallest (32 kb) and only inherited deletion included two additional centromeric genes and was not associated with ID. Three larger deletions (264–314 kb) that included at least five further centromeric genes were associated with moderate ID, suggesting that deletion of one or more of these five genes causes ID. The individual with the most severe ID had a more telomerically extending deletion, including CIC , a known ID gene. Children found to harbor ERF deletions should be referred for craniofacial assessment, to exclude occult raised intracranial pressure.