Replication of GWAS loci revealed the moderate effect of TNRC6B locus on susceptibility of Saudi women to develop uterine leiomyomas.

AIM: Uterine leiomyomas (UL) are smooth muscular nodes, whose growth is dependant up on the complex interplay of hormones with genes and uterine physiology. Global statistics indicate the role of ethnic and racial background as contributory factors for UL development. Owing to the lack of data, this study aimed to examine the association between genetic polymorphisms and susceptibility of Arab women of developing UL. METHODS: We genotyped 105 UL patients and 112 healthy controls for five genetic polymorphisms through real time PCR method. The strength of the association between genotype and allele frequencies with risk of developing UL was tested with their χ2 and odds ratio (OR) values. The synergistic cooperation between genetic polymorphisms was estimated through multifactor dimensionality reduction assay. RESULTS: We found that Saudi women with the AG genotype for the rs12484776 polymorphism are at a 2.6-fold higher risk of developing UL compared to those with other genotypes (OR, 2.69; 95% confidence interval [CI]: 1.45-5.00; P < 0.001). This significance persisted even under co-dominant models (i.e., AA vs GG + AG [OR, 2.74; 95%CI: 1.48-5.08; P = 0.001; and AG vs GG + AG [OR, 2.41; 95% CI: 1.33-4.39; P = 0.003). Genotype distribution frequencies for rs1056836, rs7913069, rs2280543, and rs4247357 were not shown to elevate the disease risk (for all tests P > 0.05). CONCLUSION: The rs12484776 significantly contributes to UL risk among Saudi women, both in single and also in synergistic cooperation with rs2280543, rs7913069, and rs1056836 markers. Our results have yielded mixed findings in replicating European- and Japanese-specific UL genetic susceptibility loci among a geographically and culturally distinct population of the Saudi Arabian Peninsula.

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women.

MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients.

Histopathological pattern of pediatric renal diseases: a study from a university hospital in western Saudi Arabia.

To study the clinical indications and histopathological pattern of renal biopsies and renal resection specimens in the pediatric age group (birth to 17 years) in a large academic center in western Saudi Arabia. A retrospective review of the computerized database of the Pathology Department at King Abdul Aziz University Hospital (KAUH) was carried out on the final pathology reports of all children of the age of 17 years and below who either had ultrasound-guided renal biopsies or partial or total renal resections during the period between January 1995 and December 2008. All the specimens were reported by our pathology department. The most common clinical indication in the study group (242) is nephrotic syndrome (117, 48.3%), followed by systemic lupus erythromatosis for staging (30, 12.4%), nephritic syndrome (27, 11.1%) and renal mass for histological diagnosis (17, 7.0%). The most frequently reported pathological diagnosis was renal glomerulopathies, constituting 183 cases (n = 183, 75.6%) of the total number of pathology reports reviewed. Primary glomerulopathies were more common (n = 155, 88.4%) than the secondary ones (n = 28, 11.6%). The second most common pediatric renal pathology in this study was renal neoplasms (14, 5.7%). Vascular renal diseases and renal glomerulosclerosis ranked as the third pathological diagnosis in order of frequency in this study, with ten cases (10, 4.1%). The most common clinical indication for renal tissue sampling in this study is nephrotic syndrome and the most frequently detected pathology is glomerulonephritis. Larger multicentre studies are needed to further study pediatric nephropathies.

Intratesticular borderline serous tumor.

Neoplasms resembling ovarian serous tumors rarely arise in the male genital organs. Müllerian histogenesis of this tumor has been suggested. We report a case of an intratesticular borderline serous tumor accidentally discovered during the course of a preoperative workup in a 72-year-old man admitted for left upper lobectomy for squamous cell carcinoma of the lung.