Journal article
Contributions of PTCH gene variants to isolated cleft lip and palate
The Cleft palate-craniofacial journal, Vol.43(1), pp.21-29
2006
DOI: 10.1597/04-169r.1
PMCID: PMC2151847
PMID: 16405370
Abstract
Objective: Mutations in patched (PTCH) cause the nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome. Nevoid basal cell carcinoma syndrome may present with developmental anomalies, including rib and craniofacial abnormalities, and predisposes to several tumor types, including basal cell carcinoma and medulloblastoma. Cleft palate is found in 4% of individuals with nevoid basal cell carcinoma syndrome. Because there might be specific sequence alterations in PTCH that limit expression to orofacial clefting, a genetic study of PTCH was undertaken in cases with cleft lip and/or palate (CL/P) known not to have nevoid basal cell carcinoma syndrome.
Results: Seven new normal variants spread along the entire gene and three missense mutations were found among cases with cleft lip and/or palate. One of these variants (P295S) was not found in any of 1188 control samples. A second variant was found in a case and also in 1 of 1119 controls. The third missense (S827G) was found in 5 of 1369 cases and in 5 of 1104 controls and is likely a rare normal variant. Linkage and linkage desequilibrium also was assessed using normal variants in and adjacent to the PTCH gene in 220 families (1776 individuals), each with two or more individuals with isolated clefting. Although no statistically significant evidence of linkage (multipoint HLOD peak = 2.36) was uncovered, there was borderline evidence of significant transmission distortion for one haplotype of two single nucleotide polymorphisms located within the PTCH gene (p = .08).
Conclusion: Missense mutations in PTCH may be rare causes of isolated cleft lip and/or palate. An as yet unidentified variant near PTCH may act as a modifier of cleft lip and/or palate.
Details
- Title: Subtitle
- Contributions of PTCH gene variants to isolated cleft lip and palate
- Creators
- M. A MANSILLA - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United StatesM. E COOPER - Center for Craniofacial and Dental Genetics, Division of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United StatesT GOLDSTEIN - Center for Craniofacial and Dental Genetics, Division of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United StatesE. E CASTILLA - Estudio Latinoamericano de Colaborativo Malformaciones Congénitas (ECLAMC) at the Department of Genetics, Fiocruz, BrazilJ. S LOPEZ CAMELO - Estudio Latinoamericano de Colaborativo Mal formaciones Congénitas (ECLAMC) at Instituto Multidisciplinario de Biología Celular (IMBICE), Buenos Aires, ArgentinaM. L MARAZITA - Center for Craniofacial and Dental Genetics, Division of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United StatesJ. C MURRAY - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- The Cleft palate-craniofacial journal, Vol.43(1), pp.21-29
- DOI
- 10.1597/04-169r.1
- PMID
- 16405370
- PMCID
- PMC2151847
- NLM abbreviation
- Cleft Palate Craniofac J
- ISSN
- 1055-6656
- eISSN
- 1545-1569
- Publisher
- American Cleft Palate-Craniofacial Association; Chapel, Hill, NC
- Language
- English
- Date published
- 2006
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
- Record Identifier
- 9984025356402771
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