Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Jeremy Parr

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Ceroni F, Simpson NH, Francks C, Baird G, Conti-Ramsden G, Clark A, Bolton PF, Hennessy ER, Donnelly P, Bentley DR, Martin H, IMGSAC, SLI Consortium, WGS500 Consortium, Parr J, Pagnamenta AT, Maestrini E, Bacchelli E, Newbury DF, Fisher SE

Publication type: Article

Publication status: Published

Journal: European Journal of Human Genetics

Year: 2014

Volume: 22

Issue: 10

Pages: 1165-1171

Print publication date: 01/10/2014

Online publication date: 12/02/2014

Acceptance date: 18/12/2013

Date deposited: 05/03/2015

ISSN (print): 1018-4813

ISSN (electronic): 1476-5438

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ejhg.2014.4

DOI: 10.1038/ejhg.2014.4


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share