Background: Gorlin syndrome is a rare autosomal-dominant disorder characterized by a wide range of developmental abnormalities and various tumors. The syndrome is caused by mutations in PTCH1, a tumor suppressor gene located at 9q22.32. We describe a Gorlin syndrome case with typical features of the syndrome and no mutations in PTCH1, but with a large deletion of the 9q22 region that has rarely been described. Objective: To fully characterize the large deletion in the patient. Methods: In order to map the size and position of the deletion, we developed quantitative multiplex fluorescent PCR with polymorphic markers surrounding the PTCH1 gene, followed by long-range PCR and sequencing. Results: The deleted segment of 4.5 Mb in the 9q22.32–q22.33 region was determined, and included the entire PTCH1, its promoter and 22 OMIM genes. Conclusion: We suggest that screening for large deletions should be included in standard mutation screening for Gorlin syndrome patients.

High A, Zedan W: Basal cell nevus syndrome. Curr Opin Oncol 2005;17:160–166.
Gorlin RJ: Nevoid basal cell carcinoma (Gorlin) syndrome: unanswered issues. J Lab Clin Med 1999;134:551–552.
Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, Bale AE, Bale SJ: Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299–308.
Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE: Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996;85:841–851.
Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP: Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996;272:1668–1671.
Klein RD, Dykas DJ, Bale AE: Clinical testing for the nevoid basal cell carcinoma syndrome in a DNA diagnostic laboratory. Genet Med 2005;7:611–619.
Reifenberger J, Wolter M, Knobbe CB, Köhler B, Schönicke A, Scharwächter C, Kumar K, Blaschke B, Ruzicka T, Reifenberger G: Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. Br J Dermatol 2005;152:43–51.
Lupi O: Correlations between the Sonic Hedgehog pathway and basal cell carcinoma. Int J Dermatol 2007;46:1113–1117.
Pietsch T, Waha A, Koch A, Kraus J, Albrecht S, Tonn J, Sörensen N, Berthold F, Henk B, Schmandt N, Wolf HK, von Deimling A, Wainwright B, Chenevix-Trench G, Wiestler OD, Wicking C: Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res 1997;57:2085–2088.
Levanat S, Pavelic B, Crnic I, Oreskovic S, Manojlovic S: Involvement of PTCH gene in various noninflammatory cysts. J Mol Med 2000;78:140–146.
Levanat S, Musani V, Komar A, Oreskovic S: Role of the hedgehog/patched signaling pathway in oncogenesis: a new polymorphism in the PTCH gene in ovarian fibroma. Ann NY Acad Sci 2004;1030:134–143.
Pavelic B, Levanat S, Crnic I, Kobler P, Anic I, Manojlovic S, Sutalo J: PTCH gene altered in dentigerous cysts. J Oral Pathol Med 2001;30:569–576.
Fujii K, Kohno Y, Sugita K, Nakamura M, Moroi Y, Urabe K, Furue M, Yamada M, Miyashita T: Mutations in the human homologue of Drosophila patched in Japanese nevoid basal cell carcinoma syndrome patients. Hum Mutat 2003;21:451–452.
Fan Z, Li J, Du J, Zhang H, Shen Y, Wang CY, Wang S: A missense mutation in PTCH2 underlies dominantly inherited in a Chinese family. J Med Genet 2008;45:303–308.
Situm M, Levanat S, Crnic I, Pavelic B, Macan D, Grgurević J, Mubrin-Koncar M, Lipozencic J: Involvement of patched (PTCH) gene in Gorlin syndrome and related disorders: three family cases. Croat Med J 1999;40:533–538.
van der Heijden MS, Yeo CJ, Hruban RH, Kern SE: Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res 2003;63:2585–2588.
Rozen S, Skaletsky HJ: Primer3 on the WWW for general users and for biologist programmers; in Krawetz S, Misener S (eds): Bioinformatics Methods and Protocols: Methods in Molecular Biology. Totowa, Humana Press, 2000, pp 365–386.
Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G: Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident. Am J Hum Genet 1997;60:21–26.
Fujii K, Ishikawa S, Uchikawa H, Komura D, Shapero MH, Shen F, Hung J, Arai H, Tanaka Y, Sasaki K, Kohno Y, Yamada M, Jones KW, Aburatani H, Miyashita T: High-density oligonucleotide array with sub-kilobase resolution reveals breakpoint information of submicroscopic deletions in nevoid basal cell carcinoma syndrome. Hum Genet 2007;122:459–466.
Boonen SE, Stahl D, Kreiborg S, Rosenberg T, Kalscheuer V, Larsen LA, Tommerup N, Brøndum-Nielsen K, Tümer Z: Delineation of an interstitial 9q22 deletion in basal cell nevus syndrome. Am J Med Genet A 2005;132:324–328.
Shimkets R, Gailani MR, Siu VM, Yang-Feng T, Pressman CL, Levanat S, Goldstein A, Dean M, Bale AE: Molecular analysis of chromosome 9q deletions in two Gorlin syndrome patients. Am J Hum Genet 1996;59:417–422.
Olivieri C, Maraschio P, Caselli D, Martini C, Beluffi G, Maserati E, Danesino C: Interstitial deletion of chromosome 9, int del(9)(9q22.31-q31.2), including the genes causing multiple basal cell nevus syndrome and Robinow/brachydactyly 1 syndrome. Eur J Pediatr 2003;162:100–103.
Midro AT, Panasiuk B, Tümer Z, Stankiewicz P, Silahtaroglu A, Lupski JR, Zemanova Z, Stasiewicz-Jarocka B, Hubert E, Tarasów E, Famulski W, Zadrozna-Tołwińska B, Wasilewska E, Kirchhoff M, Kalscheuer V, Michalova K, Tommerup N: Interstitial deletion 9q22.32-q33.2 associated with additional familial translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin-Goltz syndrome and features of Nail-Patella syndrome. Am J Med Genet 2004;124A:179–191.
Cajaiba MM, Bale AE, Alvarez-Franco M, McNamara J, Reyes-Múgica M: Rhabdomyosarcoma, Wilms tumor, and deletion of the patched gene in Gorlin syndrome. Nat Clin Pract Oncol 2006;3:575–580.
Chen CP, Lin SP, Wang TH, Chen YJ, Chen M, Wang W: Perinatal findings and molecular cytogenetic analyses of de novo interstitial deletion of 9q (9q22.3–>q31.3) associated with Gorlin syndrome. Prenat Diagn 2006;26:725–729.
Nowakowska B, Kutkowska-Kaźmierczak A, Stankiewicz P, Bocian E, Obersztyn E, Ou Z, Cheung SW, Cai WW: A girl with deletion 9q22.1-q22.32 including the PTCH and ROR2 genes identified by genome-wide array-CGH. Am J Med Genet 2007;143A:1885–1889.
Haniffa MA, Leech SN, Lynch SA, Simpson NB: NBCCS secondary to an interstitial chromosome 9q deletion. Clin Exp Dermatol 2004;29:542–544.
Soufir N, Gerard B, Portela M, Brice A, Liboutet M, Saiag P, Descamps V, Kerob D, Wolkenstein P, Gorin I, Lebbe C, Dupin N, Crickx B, Basset-Seguin N, Grandchamp B: PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study. Br J Cancer 2006;95:548–553.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.