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

Research output: Contribution to journalLetter

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Abstract

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
DOIs
Publication statusPublished - 2014

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Methylation
Language
Penetrance
Phenotype

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

In: EJHG : European journal of human genetics : the official journal of the European Society of Human Genetics. , 2014.

Research output: Contribution to journalLetter

Ceroni, F, Simpson, NH, Francks, C, Baird, G, Conti-Ramsden, G, Clark, A, Bolton, PF, Hennessy, ER, Donnelly, P, Bentley, DR, Martin, H, Parr, J, Pagnamenta, AT, Maestrini, E, Bacchelli, E, Fisher, SE, Newbury, DF & IMGSAC 2014, 'Reply to Pembrey et al: 'ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis'', EJHG : European journal of human genetics : the official journal of the European Society of Human Genetics. . https://doi.org/10.1038/ejhg.2014.275
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 ; IMGSAC. / Reply to Pembrey et al: 'ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis'. In: EJHG : European journal of human genetics : the official journal of the European Society of Human Genetics. . 2014.
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title = "Reply to Pembrey et al: 'ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis'",
abstract = "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.",
author = "Fabiola Ceroni and Simpson, {Nuala H} and Clyde Francks and Gillian Baird and Gina Conti-Ramsden and Ann Clark and Bolton, {Patrick F} and Hennessy, {Elizabeth R} and Peter Donnelly and Bentley, {David R} and Hilary Martin and Jeremy Parr and Pagnamenta, {Alistair T} and Elena Maestrini and Elena Bacchelli and Fisher, {Simon E} and Newbury, {Dianne F} and IMGSAC",
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T1 - Reply to Pembrey et al: 'ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis'

AU - Ceroni, Fabiola

AU - Simpson, Nuala H

AU - Francks, Clyde

AU - Baird, Gillian

AU - Conti-Ramsden, Gina

AU - Clark, Ann

AU - Bolton, Patrick F

AU - Hennessy, Elizabeth R

AU - Donnelly, Peter

AU - Bentley, David R

AU - Martin, Hilary

AU - Parr, Jeremy

AU - Pagnamenta, Alistair T

AU - Maestrini, Elena

AU - Bacchelli, Elena

AU - Fisher, Simon E

AU - Newbury, Dianne F

AU - IMGSAC

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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DO - 10.1038/ejhg.2014.275

M3 - Letter

C2 - 25537359

JO - EJHG : European journal of human genetics : the official journal of the European Society of Human Genetics.

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SN - 1018-4813

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