Prediction of liability to orofacial clefting using genetic and craniofacial data from parents

Peter A. Mossey, Reynir Arngrimsson, John McColl, Gill M. Vintiner, J. Michael Connor

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background - Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. Objective - To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods - Polymorphisms at the transforming growth factor alpha (TGFα) locus in 83 parents of children with non-syndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. Results - Parents of children with CL(P) and CP showed an increased frequency of the TGFα/TaqI C2 allele (RR = 4.10, p = 0.009) relative to the comparison group. Also the TGFα/BamHI A1 allele was more prevalent in the CP parents. Multivariate statistical analysis - Using stepwise logistic regression analysis the TGFα/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFα/BamHI and TGFα/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3% could be correctly classified. By adding information on craniofacial measurements in the parents, 76% of CP and 94% of CL(P) parents could be correctly classified. Conclusions - This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFα locus may modify the risk for CP and CL(P).

Original languageEnglish
Pages (from-to)371-378
Number of pages8
JournalJournal of Medical Genetics
Volume35
Issue number5
DOIs
Publication statusPublished - 21 May 1998

Fingerprint

Cleft Palate
Transforming Growth Factor alpha
Parents
Genotype
Alleles
Cephalometry
Cleft Lip
Multivariate Analysis
Logistic Models
Regression Analysis

Keywords

  • Cephalometrics
  • Orofacial clefts
  • TGFα

Cite this

Mossey, Peter A. ; Arngrimsson, Reynir ; McColl, John ; Vintiner, Gill M. ; Connor, J. Michael. / Prediction of liability to orofacial clefting using genetic and craniofacial data from parents. In: Journal of Medical Genetics. 1998 ; Vol. 35, No. 5. pp. 371-378.
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abstract = "Background - Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. Objective - To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods - Polymorphisms at the transforming growth factor alpha (TGFα) locus in 83 parents of children with non-syndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. Results - Parents of children with CL(P) and CP showed an increased frequency of the TGFα/TaqI C2 allele (RR = 4.10, p = 0.009) relative to the comparison group. Also the TGFα/BamHI A1 allele was more prevalent in the CP parents. Multivariate statistical analysis - Using stepwise logistic regression analysis the TGFα/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFα/BamHI and TGFα/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3{\%} could be correctly classified. By adding information on craniofacial measurements in the parents, 76{\%} of CP and 94{\%} of CL(P) parents could be correctly classified. Conclusions - This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFα locus may modify the risk for CP and CL(P).",
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Prediction of liability to orofacial clefting using genetic and craniofacial data from parents. / Mossey, Peter A.; Arngrimsson, Reynir; McColl, John; Vintiner, Gill M.; Connor, J. Michael.

In: Journal of Medical Genetics, Vol. 35, No. 5, 21.05.1998, p. 371-378.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prediction of liability to orofacial clefting using genetic and craniofacial data from parents

AU - Mossey, Peter A.

AU - Arngrimsson, Reynir

AU - McColl, John

AU - Vintiner, Gill M.

AU - Connor, J. Michael

PY - 1998/5/21

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N2 - Background - Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. Objective - To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods - Polymorphisms at the transforming growth factor alpha (TGFα) locus in 83 parents of children with non-syndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. Results - Parents of children with CL(P) and CP showed an increased frequency of the TGFα/TaqI C2 allele (RR = 4.10, p = 0.009) relative to the comparison group. Also the TGFα/BamHI A1 allele was more prevalent in the CP parents. Multivariate statistical analysis - Using stepwise logistic regression analysis the TGFα/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFα/BamHI and TGFα/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3% could be correctly classified. By adding information on craniofacial measurements in the parents, 76% of CP and 94% of CL(P) parents could be correctly classified. Conclusions - This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFα locus may modify the risk for CP and CL(P).

AB - Background - Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. Objective - To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods - Polymorphisms at the transforming growth factor alpha (TGFα) locus in 83 parents of children with non-syndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. Results - Parents of children with CL(P) and CP showed an increased frequency of the TGFα/TaqI C2 allele (RR = 4.10, p = 0.009) relative to the comparison group. Also the TGFα/BamHI A1 allele was more prevalent in the CP parents. Multivariate statistical analysis - Using stepwise logistic regression analysis the TGFα/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFα/BamHI and TGFα/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3% could be correctly classified. By adding information on craniofacial measurements in the parents, 76% of CP and 94% of CL(P) parents could be correctly classified. Conclusions - This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFα locus may modify the risk for CP and CL(P).

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