Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/39321
Type
ArticleCopyright
Restricted access
Embargo date
2025-01-01
Collections
- IOC - Artigos de Periódicos [12363]
Metadata
Show full item record
CONTRIBUTIONS OF PTCH GENE VARIANTS TO ISOLATED CLEFT LIP AND PALATE
Author
Affilliation
University of Iowa. Department of Pediatrics. Iowa City, Iowa, USA.
University of Pittsburgh. School of Dental Medicine. Division of Oral Biology. Center for Craniofacial and Dental Genetics. Pittsburgh, Pennsylvania, USA.
University of Pittsburgh. School of Dental Medicine. Division of Oral Biology. Center for Craniofacial and Dental Genetics. Pittsburgh, Pennsylvania, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Genética. Estudio Latinoamericano de Colaborativo Malformaciones Congénitas. Rio de Janeiro, RJ, Brasil / Consejo Nacional de Investigaciones Científicas y Técnicas. Argentina.
Estudio Latinoamericano de Colaborativo Malformaciones Congénitas at Instituto Multidisciplinario de Biología Celular. Buenos Aires, Argentina.
University of Pittsburgh. School of Dental Medicine. Division of Oral Biology. Center for Craniofacial and Dental Genetics. Pittsburgh, Pennsylvania, USA / University of Pittsburgh. Graduate School of Public Health. Department of Human Genetics. Pittsburgh, Pennsylvania, USA.
University of Iowa. Department of Pediatrics. Iowa City, Iowa, USA / University of Southern Denmark, Odense, Denmark.
University of Pittsburgh. School of Dental Medicine. Division of Oral Biology. Center for Craniofacial and Dental Genetics. Pittsburgh, Pennsylvania, USA.
University of Pittsburgh. School of Dental Medicine. Division of Oral Biology. Center for Craniofacial and Dental Genetics. Pittsburgh, Pennsylvania, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Genética. Estudio Latinoamericano de Colaborativo Malformaciones Congénitas. Rio de Janeiro, RJ, Brasil / Consejo Nacional de Investigaciones Científicas y Técnicas. Argentina.
Estudio Latinoamericano de Colaborativo Malformaciones Congénitas at Instituto Multidisciplinario de Biología Celular. Buenos Aires, Argentina.
University of Pittsburgh. School of Dental Medicine. Division of Oral Biology. Center for Craniofacial and Dental Genetics. Pittsburgh, Pennsylvania, USA / University of Pittsburgh. Graduate School of Public Health. Department of Human Genetics. Pittsburgh, Pennsylvania, USA.
University of Iowa. Department of Pediatrics. Iowa City, Iowa, USA / University of Southern Denmark, Odense, Denmark.
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.
Share