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Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2),...

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Autores principales: Ceroni, Fabiola, Simpson, Nuala H, Francks, Clyde, Baird, Gillian, Conti-Ramsden, Gina, Clark, Ann, Bolton, Patrick F, Hennessy, Elizabeth R, Donnelly, Peter, Bentley, David R, Martin, Hilary, Parr, Jeremy, Pagnamenta, Alistair T, Maestrini, Elena, Bacchelli, Elena, Fisher, Simon E, Newbury, Dianne F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169542/
https://www.ncbi.nlm.nih.gov/pubmed/24518835
http://dx.doi.org/10.1038/ejhg.2014.4
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author Ceroni, Fabiola
Simpson, Nuala H
Francks, Clyde
Baird, Gillian
Conti-Ramsden, Gina
Clark, Ann
Bolton, Patrick F
Hennessy, Elizabeth R
Donnelly, Peter
Bentley, David R
Martin, Hilary
Parr, Jeremy
Pagnamenta, Alistair T
Maestrini, Elena
Bacchelli, Elena
Fisher, Simon E
Newbury, Dianne F
author_facet Ceroni, Fabiola
Simpson, Nuala H
Francks, Clyde
Baird, Gillian
Conti-Ramsden, Gina
Clark, Ann
Bolton, Patrick F
Hennessy, Elizabeth R
Donnelly, Peter
Bentley, David R
Martin, Hilary
Parr, Jeremy
Pagnamenta, Alistair T
Maestrini, Elena
Bacchelli, Elena
Fisher, Simon E
Newbury, Dianne F
author_sort Ceroni, Fabiola
collection PubMed
description Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2), encompassing exon 5, in an individual with severe receptive and expressive language impairment. The microdeletion was not found in the proband's affected sister or her brother who had mild language impairment. However, it was inherited from both parents, each of whom carries a heterozygous microdeletion and has a history of language problems. The microdeletion falls within the AUTS1 locus, a region linked to autistic spectrum disorders (ASDs). Moreover, ZNF277 is adjacent to the DOCK4 and IMMP2L genes, which have been implicated in ASD. We screened for the presence of ZNF277 microdeletions in cohorts of children with SLI or ASD and panels of control subjects. ZNF277 microdeletions were at an increased allelic frequency in SLI probands (1.1%) compared with both ASD family members (0.3%) and independent controls (0.4%). We performed quantitative RT-PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in individuals carrying either an IMMP2L_DOCK4 microdeletion or a ZNF277 microdeletion. Although ZNF277 microdeletions reduce the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Conversely, IMMP2L_DOCK4 microdeletions do not affect the expression levels of ZNF277. We postulate that ZNF277 microdeletions may contribute to the risk of language impairments in a manner that is independent of the autism risk loci previously described in this region.
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spelling pubmed-41695422014-10-01 Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment Ceroni, Fabiola Simpson, Nuala H Francks, Clyde Baird, Gillian Conti-Ramsden, Gina Clark, Ann Bolton, Patrick F Hennessy, Elizabeth R Donnelly, Peter Bentley, David R Martin, Hilary Parr, Jeremy Pagnamenta, Alistair T Maestrini, Elena Bacchelli, Elena Fisher, Simon E Newbury, Dianne F Eur J Hum Genet Article Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2), encompassing exon 5, in an individual with severe receptive and expressive language impairment. The microdeletion was not found in the proband's affected sister or her brother who had mild language impairment. However, it was inherited from both parents, each of whom carries a heterozygous microdeletion and has a history of language problems. The microdeletion falls within the AUTS1 locus, a region linked to autistic spectrum disorders (ASDs). Moreover, ZNF277 is adjacent to the DOCK4 and IMMP2L genes, which have been implicated in ASD. We screened for the presence of ZNF277 microdeletions in cohorts of children with SLI or ASD and panels of control subjects. ZNF277 microdeletions were at an increased allelic frequency in SLI probands (1.1%) compared with both ASD family members (0.3%) and independent controls (0.4%). We performed quantitative RT-PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in individuals carrying either an IMMP2L_DOCK4 microdeletion or a ZNF277 microdeletion. Although ZNF277 microdeletions reduce the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Conversely, IMMP2L_DOCK4 microdeletions do not affect the expression levels of ZNF277. We postulate that ZNF277 microdeletions may contribute to the risk of language impairments in a manner that is independent of the autism risk loci previously described in this region. Nature Publishing Group 2014-10 2014-02-12 /pmc/articles/PMC4169542/ /pubmed/24518835 http://dx.doi.org/10.1038/ejhg.2014.4 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Article
Ceroni, Fabiola
Simpson, Nuala H
Francks, Clyde
Baird, Gillian
Conti-Ramsden, Gina
Clark, Ann
Bolton, Patrick F
Hennessy, Elizabeth R
Donnelly, Peter
Bentley, David R
Martin, Hilary
Parr, Jeremy
Pagnamenta, Alistair T
Maestrini, Elena
Bacchelli, Elena
Fisher, Simon E
Newbury, Dianne F
Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment
title Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment
title_full Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment
title_fullStr Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment
title_full_unstemmed Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment
title_short Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment
title_sort homozygous microdeletion of exon 5 in znf277 in a girl with specific language impairment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169542/
https://www.ncbi.nlm.nih.gov/pubmed/24518835
http://dx.doi.org/10.1038/ejhg.2014.4
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