Reply to Pembrey et al: 'ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis'

Fabiola Ceroni, Nuala H Simpson, Clyde Francks, Gillian Baird, Gina Conti-Ramsden, Ann Clark, Patrick F Bolton, Elizabeth R Hennessy, Peter Donnelly, David R Bentley, Hilary Martin, Jeremy Parr, Alistair T Pagnamenta, Elena Maestrini, Elena Bacchelli, Simon E Fisher, Dianne F Newbury, IMGSAC

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2 Citations (Scopus)


In a recent paper, we described a homozygous exonic microdeletion in ZNF277 in a girl with specific language impairment (SLI). This microdeletion was also identified in the heterozygous form in eight families of the SLI Consortium (SLIC) cohort and four families with ASD cases from the IMGSAC Cohort. We observed an increased allelic frequency of ZNF277 microdeletions in SLI probands (1.1%) compared with both ASD family members (0.3%) and unrelated controls (0.4%), suggesting that these microdeletions might be a risk factor for SLI. However, as the ZNF277 microdeletions showed incomplete segregation with the SLI phenotype, as they were also identified in unaffected family members and, in some cases, they were not inherited by the affected children (reverse discordance), we hypothesised that these CNVs might contribute to the SLI susceptibility in a complex manner, acting as a risk factor with a reduced penetrance.
Original languageEnglish
Number of pages1
JournalEJHG : European journal of human genetics : the official journal of the European Society of Human Genetics.
Early online date24 Dec 2014
Publication statusPublished - 2014


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