Title: A novel in-frame deletion affecting the BAR domain of OPHN1 in a family with intellectual disability and hippocampal alterations
Authors: Santos-Rebouças, Cíntia Barros ×
Belet, Stefanie
Guedes de Almeida, Luciana
Ribeiro, Márcia Gonçalves
Medina-Acosta, Enrique
Bahia, Paulo Roberto Valle
Alves da Silva, Antônio Francisco
Lima Dos Santos, Flávia
Borges de Lacerda, Glenda Corrêa
Pimentel, Márcia Mattos Gonçalves
Froyen, Guy #
Issue Date: May-2014
Publisher: Karger
Series Title: European Journal of Human Genetics vol:22 issue:5 pages:644-651
Article number: 10.1038/ejhg.2013.216
Abstract: Oligophrenin-1 (OPHN1) is one of at least seven genes located on chromosome X that take part in Rho GTPase-dependent signaling pathways involved in X-linked intellectual disability (XLID). Mutations in OPHN1 were primarily described as an exclusive cause of non-syndromic XLID, but the re-evaluation of the affected individuals using brain imaging displayed fronto-temporal atrophy and cerebellar hypoplasia as neuroanatomical marks. In this study, we describe clinical, genetic and neuroimaging data of a three generation Brazilian XLID family co-segregating a novel intragenic deletion in OPHN1. This deletion results in an in-frame loss of exon 7 at transcription level (c.781_891del; r.487_597del), which is predicted to abolish 37 amino acids from the highly conserved N-terminal BAR domain of OPHN1. cDNA expression analysis demonstrated that the mutant OPHN1 transcript is stable and no abnormal splicing was observed. Features shared by the affected males of this family include neonatal hypotonia, strabismus, prominent root of the nose, deep set eyes, hyperactivity and instability/intolerance to frustration. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia and cystic dilatation of the cisterna magna in all affected males. Interestingly, hippocampal alterations that have not been reported in patients with loss-of-function OPHN1 mutations were found in three affected individuals, suggesting an important function for the BAR domain in the hippocampus. This is the first description of an in-frame deletion within the BAR domain of OPHN1 and could provide new insights into the role of this domain in relation to brain and cognitive development or function.European Journal of Human Genetics advance online publication, 9 October 2013; doi:10.1038/ejhg.2013.216.
ISSN: 1018-4813
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Human Genome Laboratory
× corresponding author
# (joint) last author

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