1. Reply to pembrey et al: 'Znf277 microdeletions, specific language impairment and the meiotic mismatch methylation (3m) hypothesis'
- Author
-
Ceroni, F., Simpson, N.H., Francks, C., Baird, G., Conti-Ramsden, G., Clark, A., Bolton, P.F., Hennessy, E.R., Donnelly, P, Bentley, D.R., Martin, H., Parr, J., Pagnamenta, A.T., Maestrini, E., Bacchelli, E., Fisher, S.E., Newbury, D.F., Imgsac, ., Consrtium, S.L.I., Consortium, W.G.S., 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., and Newbury, Dianne F.
- Subjects
Proband ,Male ,Neuroinformatics ,medicine.medical_specialty ,Letter ,DNA-Binding Protein ,Exon ,Biology ,Specific language impairment ,behavioral disciplines and activities ,Language Development Disorder ,03 medical and health sciences ,Genetic linkage ,parasitic diseases ,medicine ,Genetics ,Humans ,Language Development Disorders ,Risk factor ,Allele frequency ,Genetics (clinical) ,030304 developmental biology ,Sequence Deletion ,0303 health sciences ,030305 genetics & heredity ,Exons ,medicine.disease ,Penetrance ,DNA-Binding Proteins ,Cohort ,Medical genetics ,lipids (amino acids, peptides, and proteins) ,Female ,Human - Abstract
In a recent paper,1 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.
- Published
- 2015