We identified seven novel germline mutations of the PTCH gene in eight unrelat ed Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the P...We identified seven novel germline mutations of the PTCH gene in eight unrelat ed Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplifie d from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations w ere found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletio ns, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the s trong basic residue arginine was substituted by serine or glycine in highly cons erved components of the putative transmembrane domain of PTCH, and these mutatio ns may therefore affect the conformation and function of the PTCH protein. No ph enotype-genotyperelationshipswerefoundintheJapanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian pat ients.展开更多
Background: Palmoplantar keratodermas (PPK) encompass a large genetically heterogeneous group of diseases associated with hyperkeratosis of the soles andor palms that occur either isolated or in association with other...Background: Palmoplantar keratodermas (PPK) encompass a large genetically heterogeneous group of diseases associated with hyperkeratosis of the soles andor palms that occur either isolated or in association with other cutaneous and extracutaneous manifestations. Pathogenic mutations in the desmoglein 1 gene (DSG1) have recently been identified in a subset of patients with the striate type of PPK. Observation: We have identified a patient with a focal non- striated form of PPK associated with discrete troubles of keratinisation at sites exposed to mechanical trauma, such as the knees, ankles or finger knuckles, and with mild nail dystrophy. Genetic analyses disclosed a novel dominantly inherited heterozygous single base insertion in exon 3 of DSG1, 121insT, leading to a premature termination codon. The mutation was also present in the father and in a sister. Conclusion: Our observation extends the spectrum of clinical features associated with genetic defects in DSG1 and provides further evidence that perturbation of desmoglein 1 expression has a critical impact on the integrity of tissues experiencing strong mechanical stress.展开更多
文摘We identified seven novel germline mutations of the PTCH gene in eight unrelat ed Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplifie d from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations w ere found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletio ns, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the s trong basic residue arginine was substituted by serine or glycine in highly cons erved components of the putative transmembrane domain of PTCH, and these mutatio ns may therefore affect the conformation and function of the PTCH protein. No ph enotype-genotyperelationshipswerefoundintheJapanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian pat ients.
文摘Background: Palmoplantar keratodermas (PPK) encompass a large genetically heterogeneous group of diseases associated with hyperkeratosis of the soles andor palms that occur either isolated or in association with other cutaneous and extracutaneous manifestations. Pathogenic mutations in the desmoglein 1 gene (DSG1) have recently been identified in a subset of patients with the striate type of PPK. Observation: We have identified a patient with a focal non- striated form of PPK associated with discrete troubles of keratinisation at sites exposed to mechanical trauma, such as the knees, ankles or finger knuckles, and with mild nail dystrophy. Genetic analyses disclosed a novel dominantly inherited heterozygous single base insertion in exon 3 of DSG1, 121insT, leading to a premature termination codon. The mutation was also present in the father and in a sister. Conclusion: Our observation extends the spectrum of clinical features associated with genetic defects in DSG1 and provides further evidence that perturbation of desmoglein 1 expression has a critical impact on the integrity of tissues experiencing strong mechanical stress.
