Localisation of gene for the naevoid basal-cell carcinoma syndrome

Reis, André; Küster, Wolfgang; Gebel, Erika; Fuhrmann, W; Groth, W; Kuklik, Miroslaw; Wegner, Rolf-Dieter; Linss, G; Hamm, Henning; Wolff, Gerhard; Gustafson, Gösta; Bürger, Joachim; Neitzel, Heidemarie

doi:10.1016/0140-6736(92)90903-g

Cited by 85 publications

(32 citation statements)

References 3 publications

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“…In my naiveté, I thought that the sharing of positive information regarding the location of the gene or even sharing negative information might be possible, but that was not to be. Within a few months, gene mapping was accomplished simultaneously by Peter Farndon et al 2 of Birmingham, André Reis et al 3 of Berlin, and Allen Bale et al 4 of New Haven. Allen also showed that the syndrome results from the uncovering of a tumor suppressor gene at this site, which explained not only the inordinate number of basal cell carcinomas but the cardiac fibromas, fetal rhabdomyomas, medulloblastomas, ovarian fibromas, lymphomesenteric cysts, and odontogenic keratocysts.…”

Section: Nevoid Basal Cell Carcinoma Syndromementioning

confidence: 99%

Nevoid basal cell carcinoma (Gorlin) syndrome

Gorlin

2004

Genetics in Medicine

323

191

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Section: Nevoid Basal Cell Carcinoma Syndromementioning

confidence: 99%

Nevoid basal cell carcinoma (Gorlin) syndrome

Gorlin

2004

Genetics in Medicine

323

191

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“…The gene has been mapped to 9q 22.3-q31 [Gailani et al, 1992;Farndon et al, 1992;Reis et al, 1992] with no evidence for heterogeneity [Chenevix-Trench et al, 1993;Wicking et al, 1994;Compton et al, 1994;. Recently, mutations in the human homologue of Drosophila patched, PTC, have been found to cause NBCC [Hahn et al, 1966;Johnson et al 1996].…”

Section: Introductionmentioning

confidence: 99%

Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome

Goldstein²,

et al. 1997

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Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include ''coarse face'' in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the falx cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the affected individuals. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management. Am.

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“…The gene for NBCCS, which was mapped to the chromosome region 9q22.3 by genetic linkage analysis (Gailani et al, 1992;Farndon et al, 1992Farndon et al, , 1994Reis et al, 1992;Wicking et al, 1994), was recently identi®ed (Hahn et al, 1996a, b;Johnson et al, 1996) as a human homologue of Drosophila patched, a transmembrane glycoprotein involved in segment polarity patterning (Hooper and Scott, 1989). The patched gene product was found to be a receptor for sonic hedgehog (shh, Stone et al, 1996;Marigo et al, 1996) and was implicated in transcriptional regulation of the WNT and TGF-b gene families.…”

Section: Introductionmentioning

confidence: 99%

Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours

et al. 1997

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The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple developmental defects and cancer susceptibility, in particular to basal cell carcinomas (BCCs). Medulloblastomas, primitive neuroectodermal tumours (PNETs) arising in childhood, occur in about 3 ± 5% of NBCCS patients and a subset of PNETs was previously found with allelic imbalance at 9q22-q23, the region containing the gene for NBCCS (PTCH). We have analysed tumour DNA samples from 37 unrelated patients with sporadic PNETs and ®ve medulloblastoma cell lines for PTCH mutations using an exon-by-exon single strand conformation polymorphism assay. We found three missense mutations, which aect conserved residues in transmembrane domains of the gene product and in the extracellular loop implicated in binding sonic hedgehog, one 2 bp deletion and an exon skipping splice site mutation. Most mutations were associated with the absence of the wild-type allele and were found in tumours exhibiting loss of heterozygosity (LOH) at locī anking PTCH. The ®nding of LOH at 9q22-q23 in most mutated tumours while present in only three out of 26 tumours, in which a mutation was not identi®ed, implicates PTCH as the target gene in PNETs with LOH at 9q22-q23 and de®cient PTCH in the development of a subset of these tumours. Since all observed mutations were absent in the germ-line, a sporadic medulloblastoma developing as the ®rst symptom of NBCCS is likely to be a very uncommon event.

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Localisation of gene for the naevoid basal-cell carcinoma syndrome

Cited by 85 publications

References 3 publications

Nevoid basal cell carcinoma (Gorlin) syndrome

Nevoid basal cell carcinoma (Gorlin) syndrome

Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome

Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours

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