H. pylori infection of the stomach is widespread among human populations including Iranians and is considered to play a major role in the pathogenesis of gastric diseases such as peptic ulcer, adenocarcinoma, and MALT lymphoma. The association between H. pylorivirulence markers and disease has been studied in other populations around the world. The aim of this study was to investigate the distribution of H. pylori vacA and cagA genotypes and their association with clinical outcomes in Iran. H. pylori was cultured from gastric biopsy specimens obtained from 137 Iranian patients (58 with duodenal ulcer, 61 with nonulcer dyspeptic [NUD], and 18 with gastric adenocarcinoma). The vacA alleles and cagA genotypes were determined by PCR. The vacA sl allele was present in 107 of the 137 subjects (78%). Multiple strains (m1 and m2) were detected in H. pylori isolates from the patients. VacA s1 genotypes were more frequent in patients with peptic ulcer (46/58; 79%) than in NUD patients (47/61; 77%). CagA was present in 44% of the patients. NUD patients had a frequency of cagA positivity similar to that of the overall population (46%). CagA was present more frequently more than cagA-negative (20% vs. 8%, respectively) in patients with gastric carcinoma (20%) than cagA-negative in patients with gastric carcinoma (8%). This is the first comprehensive study to demonstrate the frequency of colonization with mixed strain, vacA s1, m1 and m2 as the dominant genotype in these Iranian patients, where a high rate of H. pylori infection exists and is similar to the region with a low rate of H. pylori infection. Therefore, host genetics, environmental factors, and the substantial genetic heterogeneity among different H. pylori strains may contribute to the different clinical outcomes.

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Background Whole‐exome sequencing (WES) has emerged as a successful diagnostic tool in molecular genetics laboratories worldwide. In this study, we aimed to find the potential genetic cause of skeletal disease, a heterogeneous disease, revealing the obvious short stature phenotype. In an Iranian family, we used solo‐WES in a suspected patient to decipher the potential genetic cause(s). Methods A comprehensive clinical and genotyping examination was applied to suspect the disease of the patient. The solo clinical WES was exploited, and the derived data were filtered according to the standard pipelines. In order to validate the WES finding, the region harboring the candidate variant in the CTSK gene was amplified from genomic DNA and sequenced directly by Sanger sequencing. Results Sequence analysis revealed a rare novel nonsense variant, p.(Trp320*); c.905G>A, in the CTSK gene (). In silico analysis shed light on the contribution of the variant to the pathogenicity of pycnodysostosis. This variant was confirmed by Sanger sequencing and further clinical examinations of the patient confirmed the disease. Conclusion The present study shows a rare variant of the CTSK gene, which inherited as autosomal recessive, in an Iranian male patient with pycnodysostosis. Taken together, the novel nonsense CTSK variant meets the criteria of being likely pathogenic according to the American College of Medical Genetics and Genomics‐the Association for Molecular Pathology (ACMG‐AMP) variant interpretation guidelines.

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