Medical Sequencing of Candidate Genes for Nonsyndromic Cleft Lip and Palate

Objective The purpose of this study was to determine whether the candidate genes previously studied in subjects with cleft lip, cleft palate, or both are associated with hypodontia outside the region of the cleft. Subjects One hundred twenty subjects from the Iowa Craniofacial Anomalies Research Center were selected based on the availability of both dental records and genotype information. Method The type of orofacial clefting and type and location of dental anomalies (missing teeth, supernumerary teeth, or peg laterals) were assessed by dental chart review and radiographic examination. Genotype analysis of candidate genes was performed using polymerase chain reaction/single-strand conformation polymorphism analysis. Results The prevalence of hypodontia in this sample was 47.5%, with 30.0% of subjects having missing teeth outside the cleft. There was a positive association between subjects with cleft lip or cleft lip and palate who had hypodontia outside the cleft region (compared with noncleft controls) and both muscle segment homeo box homolog 1 (MSX1) (p = .029) and transforming growth factor beta 3 (TGFB3) (p = .024). It was not possible in this analysis to determine whether this association was specifically associated with orofacial clefting combined with hypodontia or whether it was due primarily to the clefting phenotype. Conclusions In this sample, there was a significantly greater incidence of hypodontia outside the cleft region in subjects with cleft lip and palate, compared with cleft lip only or cleft palate only. Cleft lip and/or palate with hypodontia outside the cleft region was positively associated with both TGFB3 and MSX1, compared with noncleft controls.

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Faculty Opinions recommendation of Medical sequencing of candidate genes for nonsyndromic cleft lip and palate.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1029669.347517 ◽

2005 ◽

Author(s):

Terri Beaty

Keyword(s):

Candidate Genes ◽

Cleft Lip ◽

Cleft Lip And Palate

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Discordant MZ Twins With Cleft Lip and Palate: A Model for Identifying Genes in Complex Traits

Twin Research and Human Genetics ◽

10.1375/twin.8.1.39 ◽

2005 ◽

Vol 8 (1) ◽

pp. 39-46 ◽

Cited By ~ 15

Author(s):

Maria Adela Mansilla ◽

Jane Kimani ◽

Laura E. Mitchell ◽

Kaare Christensen ◽

Dorret I. Boomsma ◽

...

Keyword(s):

Dna Sequencing ◽

Candidate Genes ◽

Dna Sequences ◽

Complex Traits ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Somatic Mosaicism ◽

Interactive Effects ◽

Sequence Comparisons ◽

Mz Twins

AbstractMonozygotic (MZ) twins may be discordant for complex traits due to differential environmental exposure in utero, epigenetic variability in imprinting, X chromosome inactivation, or stochastic effects. Occasionally MZ twins may be discordant for chromosomal and single gene disorders due to somatic mosaicism. For complex traits, which are due to the interactive effects of multiple genes and environmental factors, the affected twin of a discordant MZ pair offers the possibility for identifying somatic mutations in candidate genes. DNA sequencing of candidate genes in discordant MZ twins can identify those rare etiologic mutational events responsible for the different phenotypes since the confounding effects of common single nucleotide polymorphisms are eliminated, as DNA sequences should be identical in MZ pairs. In this report we describe the extensive DNA sequencing of 18 candidate genes in a sample of MZ and dizygotic (DZ) twins with nonsyndromic cleft lip with or without cleft palate. We were unable to identify any somatic differences in approximately 34 Kb of DNA sequenced in 13 MZ pairs, for a total of approximately 900 Kb of sequence comparisons, supporting the hypothesis that nonetiologic posttwinning mutations are rare. While no etiologic variants were identified in this study, sequence comparisons of discordant MZ twins can serve as a tool for identifying etiologic mutations in clefting and other complex traits.

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