Contributions of PTCH Gene Variants to Isolated Cleft Lip and Palate

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.

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Clinical Finding and Management of 12 Orofacial Clefts Cases with Nevoid Basal Cell Carcinoma Syndrome

The Cleft Palate-Craniofacial Journal ◽

10.1597/14-323 ◽

2017 ◽

Vol 54 (3) ◽

pp. 338-342 ◽

Cited By ~ 2

Author(s):

Lee Mui Lee ◽

Lian Ma ◽

Tie Jun Li

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Diagnostic Criteria ◽

Basal Cell ◽

Clinical Management ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Clinical Phenotype ◽

Team Approach ◽

Alveolar Bone Grafting

Objective To study the phenotype and overview the clinical management on Cleft Lip and/or Palate (CL/P) with Nevoid Basal Cell Carcinoma Syndrome (NBCCS) patients in Peking University School and Hospital of Stomatology. Design Case series study. Main Outcome Measures To describe the clinical phenotype of 12 CL/P with NBCCS patients who fulfilled the diagnostic criteria as well as to explore clinical management. Results Seven cases (7/12, 58.33%) were classified as bilateral complete cleft lip and palate (BCCLP). Two cases (2/12, 16.67%) were classified as unilateral complete cleft lip and palate (UCCLP). Three cases (1/12, 8.33%) were classified as unilateral complete cleft lip (UCCL), submucosa cleft uvula (SCU), and bifid uvula (BU), respectively. The ratio of male/female was 9/3. Keratocystic odontogenic tumors (KCOTs) were presented in all 12 cases. The most common site was the mandible region (12/12, 100%) followed by the maxilla region (7/12, 58.33%). The diagnostic age of 12 NBCCS with CL/P ranged from 11 to 42 years old (usually postponed to the occurring of KCOTs). The delayed diagnosis of NBCCS can be attributed to its complicated clinical manifestations. In some cases, the mutual effect between the surgical therapy of removing KCOTs and alveolar bone grafting made the team approach (TA) of CL/P more complicated. Conclusion CL/P may become important clinical phenotype in NBCCS. The type of cleft varied, with bilateral cleft lip and palate comprising above 50%. Larger sample sizes are needed to study and confirm this result. KCOTs, as one of the most common clinical feature of NBCCS, make the diagnosis delayed and the TA more difficult because of the occurring time and site. This compels us to improve the diagnostic criteria to make an early diagnosis and explore a better therapeutic protocol for CL/P.

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Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations

Journal of Human Genetics ◽

10.1038/jhg.2009.51 ◽

2009 ◽

Vol 54 (7) ◽

pp. 398-402 ◽

Cited By ~ 7

Author(s):

Ryo Sasaki ◽

Kayoko Saito ◽

Yorikatsu Watanabe ◽

Yoshinaga Takayama ◽

Katsunori Fujii ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Gene Mutations ◽

The Novel

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Basal Cell Carcinoma Arising in a Cleft Lip Repair Scar

Dermatologic Surgery ◽

10.1046/j.1524-4725.2001.00181.x ◽

2001 ◽

Vol 27 (2) ◽

pp. 195-197 ◽

Cited By ~ 3

Author(s):

Mandy Warthan Wright ◽

Rebecca A. McCarthy ◽

Erica Bujol Kelly ◽

Steven T. Wright ◽

Richard F. Wagner

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Cleft Lip ◽

Cleft Lip Repair

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Association of chromosome 19q13.2-3 haplotypes with basal cell carcinoma: tentative delineation of an involved region using data for single nucleotide polymorphisms in two cohorts

Carcinogenesis ◽

10.1093/carcin/23.7.1149 ◽

2002 ◽

Vol 23 (7) ◽

pp. 1149-1153 ◽

Cited By ~ 31

Author(s):

E. Rockenbauer

Keyword(s):

Basal Cell Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Cell Carcinoma ◽

Basal Cell ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Using Data

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Single nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skin

Carcinogenesis ◽

10.1093/carcin/bgi381 ◽

2005 ◽

Vol 27 (8) ◽

pp. 1676-1681 ◽

Cited By ~ 56

Author(s):

R. K. Thirumaran

Keyword(s):

Dna Repair ◽

Basal Cell Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Cell Carcinoma ◽

Basal Cell ◽

Dna Repair Genes ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Repair Genes

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Potential association of single nucleotide polymorphisms in pigmentation genes with the development of basal cell carcinoma

The Journal of Dermatology ◽

10.1111/j.1346-8138.2012.01559.x ◽

2012 ◽

Vol 39 (8) ◽

pp. 693-698 ◽

Cited By ~ 11

Author(s):

Agnieszka KOSINIAK-KAMYSZ ◽

Ewelina POŚPIECH ◽

Anna WOJAS-PELC ◽

Magdalena MARCIŃSKA ◽

Wojciech BRANICKI

Keyword(s):

Basal Cell Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Cell Carcinoma ◽

Basal Cell ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Potential Association

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Telomere length, arsenic exposure and risk of basal cell carcinoma of skin

Carcinogenesis ◽

10.1093/carcin/bgz059 ◽

2019 ◽

Vol 40 (6) ◽

pp. 715-723 ◽

Cited By ~ 5

Author(s):

Nalini Srinivas ◽

Sivaramakrishna Rachakonda ◽

Thomas Hielscher ◽

Silvia Calderazzo ◽

Peter Rudnai ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Telomere Length ◽

Basal Cell ◽

Disease Risk ◽

Contrast Ratio ◽

Arsenic Exposure ◽

Exposure Group ◽

Nucleotide Polymorphisms ◽

Increased Risk

Abstract Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study, based on arsenic-exposed 528 cases with basal cell carcinoma (BCC) of skin and 533 healthy controls, we investigated effect of telomere length, measured by real-time PCR, on the disease risk. We observed a statistically significant association between decreased telomere length and increased BCC risk [odds ratio (OR) = 5.92, 95% confidence interval (CI) = 3.92 to 9.01, P < 0.0001]. Due to confounder effect of arsenic exposure, in a two-sample Mendelian randomization (MR), telomere length associated single-nucleotide polymorphisms as instrument variables violated valid assumptions; however, one-sample MR adjusted for arsenic exposure indicated an increased risk of BCC with short telomeres. The interaction between arsenic exposure and telomere length on BCC risk was statistically significant (P = 0.02). Within each tertile based on arsenic exposure, the individuals with shorter telomeres were at an increased risk of BCC, with highest risk being in the highest exposed group (OR = 16.13, 95% CI = 6.71 to 40.00, P < 0.0001), followed by those in medium exposure group and low exposure group. The combined effect of highest arsenic exposure and shortest telomeres on BCC risk (OR = 10.56, 95% CI = 5.14 to 21.70) showed a statistically significant departure from additivity (interaction contrast ratio 6.56, P = 0.03). Our results show that in the presence of arsenic exposure, decreased telomere length predisposes individuals to increased risk of BCC, with the effect being synergistic in individuals with highest arsenic exposure and shortest telomeres.

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