Gorlin Sendromlu olgularda saptanan üç yeni PTCH1 varyantı

Aslı Ece Solmaz; Hüseyin Onay

doi:10.19161/etd.886157

EN TR

Detection of three new PTCH1 variants in patients with Gorlin Syndrome

Abstract

Aim: Gorlin Syndrome (OMIM # 109400) is a rare autosomal dominant disease characterized by basal cell carcinomas (RCC), skeletal abnormalities and multiple cysts observed in the jaw. Mutations in the PTCH1 gene are responsible for 50-85% of Gorlin Syndrome. The aim of this study was to retrospectively evaluate PTCH1 gene sequence analysis in patients with clinically diagnosed Gorlin Syndrome and to delineate phenotype-genotype correlations. Materials and Methods: Four patients who referred to the Ege University Medical Faculty Hospital Medical Genetics Department due to Gorlin Syndrome were considered with mutations in PTCH1 gene and clinical findings analyzed retrospectively. Results: Four different mutations mutations (with three being novel) were detected in four patients who underwent PTCH1 gene sequence analysis. The frequency and distribution of clinical findings were evaluated. Conclusion: This is the first study from Turkey investigating PTCH1 gene mutation spectrum in Gorlin Syndrome which were identified three novel mutations. Phenotype-genotype correlation was evaluated with mutations and clinical findings.

Keywords

Gorlin Sendromlu olgularda saptanan üç yeni PTCH1 varyantı

Öz

Amaç Gorlin Sendromu (OMIM #109400), bazal hücreli karsinomalar (BHK), iskelet anomalileri ve çenede gözlenen çok sayıdaki kistlerle karakterize otozomal dominant kalıtımlı nadir bir hastalıktır. Gorlin Sendromu’nun %50-85’inden PTCH1 genindeki mutasyonlar sorumludur. Bu çalışmada klinik olarak Gorlin Sendromu tanısı düşünülen hastalarda yapılmış PTCH1 gen dizi analizlerinin retrospektif olarak değerlendirilmesi ve mutasyon saptanan hastalarda fenotip-genotip korelasyonu yapılması amaçlanmıştır. Gereç ve Yöntem XXX Üniversitesi Tıp Fakültesi Hastanesi Tıbbi Genetik Anabilim Dalı’na başvuran Gorlin Sendromu düşünülen 4 hastanın PTCH1 genindeki mutasyonları ile klinik ve laboratuvar bulguları geriye dönük olarak incelenmiştir. Bulgular PTCH1 gen dizi analizi yapılan dört hastada üçü yeni olmak üzere dört farklı mutasyon saptanmıştır. Hastalardaki klinik bulguların sıklıklıkları ve dağılımı değerlendirildi. Sonuç Bu çalışma Türkiye’de yapılan Gorlin Sendromlu olgularda PTCH1 gen mutasyon spektrumu ile ilgili ilk çalışma olup üç yeni mutasyon saptanmıştır. Saptanan mutasyonlar ve klinik bulgular ile fenotip-genotip korelasyonu değerlendirilmiştir.

Anahtar Kelimeler

Kaynakça

Satinoff MI, Wells C. Multiple basal cell naevus syndrome in ancient Egypt. Med Hist 1969; doi: 10.1017/S0025727300014563.
GORLIN RJ, GOLTZ RW. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med 1960; doi: 10.1056/NEJM196005052621803. Springate JE. The nevoid basal cell carcinoma syndrome. J Pediatr Surg 1986; 21:908–10.
Cilt 60 Sayı 1, Mart 2021 / Volume 60 Issue 1, March 2021 5
Jones EA, Sajid MI, Shenton A, Evans DG. Basal Cell Carcinomas in Gorlin Syndrome: A Review of 202 Patients. J Skin Cancer 2011; 2011: 1–6.
Bree AF, Shah MR. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet Part A 2011; 155: 2091–7.
Johnson RL, Rothman AL, Xie J, et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science (80-) 1996; doi: 10.1126/science.272.5268.1668.
Pastorino L, Ghiorzo P, Nasti S, et al. Identification of a SUFU germline mutation in a family with Gorlin syndrome. Am J Med Genet Part A 2009; doi: 10.1002/ajmg.a.32944.
Fujii K, Ohashi H, Suzuki M, et al. Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome. Fam Cancer 2013; doi: 10.1007/s10689-013-9623-1.

Evans DG, Oudit D, Smith MJ, et al. First evidence of genotype–phenotype correlations in Gorlin syndrome. J Med Genet 2017; 54: 530–6.
Smith MJ, Beetz C, Williams SG, et al. Germline Mutations in SUFU Cause Gorlin Syndrome–Associated Childhood Medulloblastoma and Redefine the Risk Associated With PTCH1 Mutations. J Clin Oncol 2014; 32: 4155–61.
11. Stone DM, Hynes M, Armanini M, et al. The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 1996; doi: 10.1038/384129a0.
Durmaz CD, Evans G, Smith MJ, Ertop P, Akay BN, Tuncall T. A Novel PTCH1 Frameshift Mutation Leading to Nevoid Basal Cell Carcinoma Syndrome. Cytogenet Genome Res 2018; 154: 57–61.
Ozcan G, Balta B, Sekerci A, et al. A novel PTCH1 gene mutation in a pediatric patient associated multiple keratocystic odontogenic tumors of the jaws and Gorlin–Goltz syndrome. Indian J Pathol Microbiol 2016; 59: 335.
Ozlu E, Karadag AS, Akalın I, et al. Novel PTCH1 Gene Mutation in a Patient with Gorlin–Goltz Syndrome. Ann Dermatol 2019; 31: S10.
Boutet N, Bignon Y-J, Drouin-Garraud V, et al. Spectrum of PTCH1 Mutations in French Patients with Gorlin Syndrome. J Invest Dermatol 2003; 121: 478–81.
HGMD database. http://www.hgmd.cf.ac.uk/ac/index.php. Acce- n.d.
Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997; 69: 299–308.
Alonso N, Cañueto J, Ciria S, et al. Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome. Br J Dermatol 2018; 178: 198–206.
Veenstra-Knol HE, Scheewe JH, Van Der Vlist GJ, Van Doorn ME, Ausems MGEM. Early recognition of basal cell naevus syndrome. Eur J Pediatr 2005; doi: 10.1007/s00431-004-1597-4