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

First Comprehensive In Silico

GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases

Antenatal diagnosis, prevalence and outcome of congenital anomalies of the kidney and urinary tract in Saudi Arabia

Objective: To study the prevalence, pattern of distribution, and the outcome of different types of kidney and urinary tract anomalies (CAKUT) diagnosed during the antenatal period. The second objective is to test the accuracy of antenatal diagnosis of CAKUT. Materials and Methods: In a cross-sectional hospital-based study, all cases diagnosed antenatally with urinary tract anomalies at King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia, were studied. The prevalence, pattern of distribution, and immediate postnatal outcomes, in addition to the accuracy of antenatal diagnosis, of those cases are reported. Results: One hundred and forty-one cases of urinary tract anomalies were antenatally diagnosed; postnatal diagnosis was confirmed in 128 cases (90.1%). The prevalence of CAKUT in our population is 3.26 per 1000 births. The most common abnormalities detected were hydronephrosis, polycystic kidney disease, multicystic dysplastic kidney, and renal agenesis, in descending order of frequency. The perinatal mortality rate among fetuses with CAKUT is 310 per 1000, the majority of these cases (90%) occurred in cases with renal parenchyma involvement. Conclusions: The prevalence of different types of CAKUT is higher than that reported in developed countries. Urinary tract anomalies can be accurately diagnosed and classified in the antenatal period using ultrasonography imaging. Antenatal diagnosis is a helpful tool in planning immediate postnatal care and deciding the place for delivery. This might prevent or slow renal function deterioration and help in early identification of patients who need early surgical intervention

Health rights knowledge among medical school students at King Abdulaziz University, Jeddah, Saudi Arabia.

Health care is a basic human right, and Saudi Arabia affirms these rights for all its citizens.To assess the knowledge of medical students regarding health rights in Saudi Arabia.This cross-sectional study was conducted at King Abdulaziz University (KAU) from September 2015 through November 2015. A questionnaire written in English collected demographic data and included questions about reproductive health care and health rights of women and patients with cancer, senility, or special needs.Of the 267 participants, 184 (68.9%) were female, and 252 (94.4%) were Saudi. Regarding consent, 87 (32.6%) and 113 (42.3%) participants believed a female patient required the consent of a male guardian to receive medical treatment or surgery, respectively, in Saudi Arabia, and only 106 (39.7%) knew that a female patient could provide consent for a caesarean section. Sixty-six (24.7%) believed that abortion is never allowed in Islam. Only 93 (34.8%) were aware that acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) patients had health rights, about half (144, 53.9%) knew that cancer patients have a right to full information, and most (181, 67.8%) believed that a patient had the right to withhold health information from his/her family. Approximately half were aware that cancer patients have the right to free medical treatment (138, 51.7%) or that health rights applied to special needs patients (137, 51.3%) and senile patients (122, 45.7%).The knowledge of KAU medical students regarding health rights of certain patient populations highlights the importance of health rights education in medical school