zohreh ataei kachoei

Bladder cancer is the most frequent malignancy that affects the urinary tract. Studies have shown different types of FGFR3 and HRAS genes mutations in human bladder cancer, with a comprehensive range of mutation number in various populations. This study aimed to determine the specific point mutations of these 2 genes among Iranian patients with bladder cancer.

In this study, 100 specimens of patients with transitional cell carcinoma were analyzed.  All samples were examined for FGFR3 and HRAS mutations using PCR and direct DNA sequencing methods 

A total of 9 pathogenic mutations and 9 polymorphisms were found in 2 exons (7 and 15) of the FGFR3 genes in patients with bladder cancer (S249Y, I633I, L645L, D646E, Y647*, D628V, P250T, Q263H, Y305H). However, no mutation was found in exon 10 of FGFR3 and exon 1 of HRAS genes.

In this study, 5 mutations were found in FGFR3 gene that have not been detected previously. There was no mutation in exon 10 of FGFR3 and exon1 of HRAS. The results of this study confirmed the association of ethnic-genetic factors in the occurrence of bladder cancer, so that these variables may not be present in all ethnic groups.

Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14. Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations.

Exons 1 and 6-7 of KRT 5 and exons 1 and 4-7 of KRT 14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools.

Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype [G96D (p.Gly96Asp) and F97I (p.Phe97Ile) in KRT5]. One of them showed a Dowling–Meara phenotype [A417P (p.Ala417Pro) and E477D (p.Glu477Asp) in KRT5] and another had a Koebner type phenotype [R397I (p.Arg397Ile) and Q444* (p.Gln444Ter) in KRT5]. A novel variant [G92E (p.Gly92Glu) in KRT5] in a double heterozygous state with a challenging variant [A413T (p.Ala413Thr) in KRT14] identified in one patient with Koebner type phenotype. Also, a previously reported mutation [I377T (p.Ile377Thr) in KRT14 gene] identified in this study.

The results of molecular data analysis showed that the most severe phenotypes were associated with mutations in highly conserved regions. In some cases, different inheritance modes were observed.