Involvement of patched (PTCH) gene in Gorlin syndrome and related disorders: three family cases.
OBJECTIVE
To find genetic alterations in PTC or other genes of the Shh/PTCH pathway in tumorous and non- tumorous samples from three families and to correlate them with the varying expression of disorders in presented nevoid basal cell carcinoma syndrome (NBCCS) phenotypes.


METHODS
DNA was extracted from archival paraffin-embedded tissues, tumor tissue or peripheral blood leukocytes, and the loss of heterozygosity (LOH) and single strand conformational polymorphism analysis was performed using PCR with primers for polymorphic 9q22.3 markers (D9S196, D9S287, D9S180, D9S127); PTCH exons 3, 6, 8, 13, 15, 16; and smo (smoothened) exon 1. G-banding tecnique was used for cytogenetic analysis of the peripheral blood lymphocytes.


RESULTS
We found a LOH for PTCH in several cases and variability in smo in one case. In one case NBCCS could reasonably be ascribed to hemizygous PTCH inactivation, while in other two families this typical correlation between the syndrome phenotype and the observed genetic alterations could not been established.


CONCLUSIONS
Further analysis of relatively sparse cases of NBCCS is needed before the symptoms of the syndrome could be convincingly explained by genetic alterations in the Shh/PTCH signalling pathway.
Situm
M
M
Department of Molecular Medicine, Rudjer Boskovi Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Levanat
S
S
Crnic
I
I
Pavelic
B
B
Macan
D
D
Grgurević
J
J
Mubrin-Koncar
M
M
Lipozencić
J
J
D000293:Adolescent; D000483:Alleles; D001478:Basal Cell Nevus Syndrome / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002869:Chromosome Aberrations / Q000235:genetics / Q000378:metabolism; D025063:Chromosome Disorders; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; D005819:Genetic Markers; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface