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Gorlin Syndrome (gorlin + syndrome)
Selected AbstractsFurther delineation of 9q22 deletion syndrome associated with basal cell nevus (Gorlin) syndrome: Report of two cases and review of the literatureCONGENITAL ANOMALIES, Issue 1 2009Kayono Yamamoto ABSTRACT Basal cell nevus syndrome (BCNS; Gorlin syndrome) is an autosomal dominant disorder, characterized by a predisposition to neoplasms and developmental abnormalities. BCNS is caused by mutations in the human homolog of the Drosophila patched gene-1, PTCH1, which is mapped on chromosome 9q22.3. Nonsense, frameshift, in-frame deletions, splice-site, and missense mutations have been found in the syndrome. Haploinsufficiency of PTCH1, which is caused by interstitial deletion of 9q22.3, is also responsible for the syndrome. To date, 19 cases with interstitial deletion of long arm of chromosome 9 involving the region of q22 have been reported. We describe two unrelated patients with some typical features of BCNS associated with deletion of 9q21.33-q31.1 and determined the boundary of the deletion by fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. The results showed that the size of deletions is between 15.33 and 16.04 Mb in patient 1 and between 18.08 and 18.54 Mb in patient 2. Although the size and breakpoints were different from those of previously reported cases, the clinical features are common to patients with 9q22 deletion associated with BCNS. Delineation of the 9q22 deletions and further consideration of the genes responsible for the characteristic manifestations may provide insight into this newly recognized deletion syndrome. [source] Concomitant ulcerative colitis and rectal cancer in a patient with Gorlin syndromeINFLAMMATORY BOWEL DISEASES, Issue 4 2009Fergal Fleming MD No abstract is available for this article. [source] An unusual ostensible example of intraoral basal cell carcinomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2009Ioannis G. Koutlas An example of oral basal cell carcinoma is presented originating on the posterior mandibular mucosa and gingiva of a 67-year-old female. Histologically, it featured a multifocal pattern. It recurred eight times in a period of 20 years. Tissue samples of the tumor were evaluated with monoclonal antibody Ber-EP4 and were compared with examples of oral mucosa, skin, oral and cutaneous squamous cell carcinoma, peripheral ameloblastoma, ameloblastoma and cutaneous basal cell carcinoma (BCC). Only neoplastic basal cells showed positive immunohistochemical staining. Additionally, microdissected neoplastic areas were evaluated for loss of heterozygosity (LOH) of the PTCH gene with markers D9S303, D9S252 and D9S287. PTCH gene mutations are reported in patients with Gorlin syndrome and sporadic cutaneous BCCs. Loss of one allele was observed with all three markers. Examples of conventional ameloblastomas did not show evidence of LOH. These observations support the inclusion of BCC in the differential diagnosis of appropriate oral mucosal neoplasms. [source] Perinatal findings and molecular cytogenetic analyses of de novo interstitial deletion of 9q (9q22.3,q31.3) associated with Gorlin syndromePRENATAL DIAGNOSIS, Issue 8 2006Chih-Ping Chen Abstract Objectives To present the perinatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 9q (9q22.3,q31.3) associated with Gorlin syndrome. Methods Amniocentesis was performed at 18 weeks' gestation on a 27-year-old woman at a community hospital because of a high Down syndrome risk of 1/178, a low maternal serum ,-fetoprotein (MSAFP) level of 0.66 multiples of the median (MoM), and a high maternal serum human chorionic gonadotrophin (MShCG) level of 3.13 MoM. The karyotype was initially determined to be 46,XY. However, fetal macrocephaly and overgrowth were found at 30 weeks' gestation. Postnatally, the infant manifested characteristic features of Gorlin syndrome. High-resolution chromosomal bandings of the peripheral blood lymphocytes, polymorphic DNA marker analysis to determine the parental origin of the deletion, array comparative genomic hybridization (CGH) to determine the extent of the chromosomal deletion, and fluorescence in situ hybridization (FISH) to determine the deletion of the PTCH gene were performed. Results The 850-band level of resolution showed an interstitial deletion of 9q (9q22.3,q31.3). The parental karyotypes were normal. The karyotype of the proband was 46,XY,del(9)(q22.3q31.3)de novo. Polymorphic DNA marker analysis revealed that the deletion was of paternal origin. Array CGH revealed that the deleted region was about 12 Mb, encompassing the segment from 9q22.32 to 9q31.3. FISH analysis using the BAC probe RP11-34D4 and the probe RP11-43505 indicated the deletion of the PTCH gene. Conclusions Fetuses with an interstitial deletion of 9q (9q22.3,q31.3) may be associated with a low level of MSAFP and a high level of MShCG in the second trimester, and sonographic findings of overgrowth and macrocephaly in the third trimester. Copyright © 2006 John Wiley & Sons, Ltd. [source] Genetics of basal cell carcinomaAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 2 2010Sally E De Zwaan ABSTRACT Basal cell carcinoma is the most common human malignancy in populations of European origin, and Australia has the highest incidence of basal cell carcinoma in the world. Great advances in the understanding of the genetics of this cancer have occurred in recent years. Mutations of the patched 1 gene (PTCH1) lead to basal cell carcinoma predisposition in Gorlin syndrome. PTCH1 is part of the hedgehog signalling pathway, and derangements within this pathway are now known to be important in the carcinogenesis of many different cancers including sporadic basal cell carcinoma. The molecular biology of the hedgehog pathway is discussed, and mouse models of basal cell carcinoma based on this pathway are explored. New developments in non-surgical treatment of basal cell carcinoma are based on this knowledge. Other genes of importance to basal cell carcinoma development include the tumour suppressor gene P53 and the melanocortin-1 receptor gene. In addition, we discuss molecules of possible importance such as the glutathione-S-transferases, DNA repair genes, cyclin-dependent kinase inhibitor 2A, Brahma and connexins. Evidence of familial aggregation of this cancer is explored and supports the possibility of genetic predisposition to this common malignancy. [source] Nonsense-associated altered splicing of the Patched gene fails to suppress carcinogenesis in Gorlin syndromeBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2008M. Laimer Summary Mutations in the gene coding for the transmembrane receptor protein Patched (PTCH) are implicated in the autosomal dominant disorder Gorlin syndrome (also known as naevoid basal cell carcinoma syndrome), characterized by congenital abnormalities and cancer predisposition. Tumour promotion is thought to be associated with aberrant function of PTCH, leading to misregulation of the hedgehog signalling network. However, the transcriptional events that underlie the reduced tumour suppression effects of PTCH have not been studied in detail. We describe a patient with Gorlin syndrome who had three molecular aberrations resulting in biallelic disruption of the PTCH gene, leading to abnormal protein expression and development of basal cell carcinoma. Remarkably, within tumour cells, the somatic nonsense mutation G1019X was associated with activation of a cryptic splice donor site, in which an in-frame deletion of the exon sequence containing the nonsense mutation occurred. However, the function of the resulting PTCH protein variant was still compromised. The pathogenetic alterations described give insights into the sequence of events leading to cellular transformation and underscore the importance of the PTCH protein in skin homeostasis. [source] Highly active antiretroviral therapy-induced regression of basal cell carcinomas in a patient with acquired immunodeficiency and Gorlin syndromeBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2006S.Y. Chan No abstract is available for this article. [source] Delayed diagnosis of Gorlin's syndrome in a renal transplant recipientAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 2 2009Katarzyna A Mackenzie ABSTRACT A 35-year-old woman was referred to the dedicated dermatology clinic for RTR. She underwent her first renal transplant at 18 years of age due to chronic renal failure following reflux nephropathy of the single right kidney (left kidney agenesis). She has since then had two further transplants. During clinical examination she was noted to have at least 16 basal cell carcinomas (BCC) and there are records in the case notes of 10 BCC having being excised and confirmed histologically in the past. By contrast, she had only had two squamous cell carcinomas (SCC) excised. She was also noted to have distinctive facial features, a kyphoscoliosis and palmar pits, and a diagnosis of Gorlin's (naevoid BCC) syndrome (GS) was made. Although immunosuppression may have contributed to the multiplicity of her BCC, the contrasting very small number of SCC is unusual in an organ transplant recipient and this alerted the authors to the diagnosis of GS. [source] | |||||||||||||