Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.

THOC6 is a part of the THO complex, which is involved in coordinating mRNA processing with export. The THO complex interacts with additional components to form the larger TREX complex (transcription export complex). Previously, a homozygous missense mutation in THOC6 in the Hutterite population was reported in association with syndromic intellectual disability. Using exome sequencing, we identified three unrelated patients with bi-allelic mutations in THOC6 associated with intellectual disability and additional clinical features. Two of the patients were compound heterozygous for a stop and a missense mutation, and the third was homozygous for a missense mutation; the missense mutations were predicted to be pathogenic by in silico analysis and modeling. Clinical features of the three newly identified patients and those previously reported are reviewed; intellectual disability is moderate to severe, and malformations are variable including renal and heart defects, cleft palate, microcephaly, and corpus callosum dysgenesis. Facial features are variable and include tall forehead, short upslanting palpebral fissures +/- deep set eyes, and a long nose with overhanging columella. These subtle facial features render the diagnosis difficult to make in isolation with certainty. Our results expand the mutational and clinical spectrum of this rare disease, confirm that THOC6 is an intellectual disability causing gene, while providing insight into the importance of the THO complex in neurodevelopment.

Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population.

Neuromuscular diseases (NMDs) include a broad range of disorders affecting muscles, nerves and neuromuscular junctions. Their overlapping phenotypes and heterogeneous genetic nature have created challenges in diagnosis which calls for the implementation of massive parallel sequencing as a candidate strategy to increase the diagnostic yield. In this study, total of 45 patients, mostly offspring of consanguineous marriages were examined using whole exome sequencing. Data analysis was performed to identify the most probable pathogenic rare variants in known NMD genes which led to identification of causal variants for 33 out of 45 patients (73.3%) in the following known genes: CAPN3, Col6A1, Col6A3, DMD, DYSF, FHL1, GJB1, ISPD, LAMA2, LMNA, PLEC1, RYR1, SGCA, SGCB, SYNE1, TNNT1 and 22 novel pathogenic variants were detected. Today, the advantage of whole exome sequencing in clinical diagnostic strategies of heterogeneous disorders is clear. In this cohort, a diagnostic yield of 73.3% was achieved which is quite high compared to the overall reported diagnostic yield of 25% to 50%. This could be explained by the consanguineous background of these patients and is another strong advantage of offering clinical exome sequencing in diagnostic laboratories, especially in populations with high rate of consanguinity.

Intersectoral collaboration to develop health equity indicators in iran.

BACKGROUND: Health equity is considered as one of the main objectives of health care systems. This study was carried out with the aim of determining health equity indicators in Iran. Through consideration of these indicators, differences in health status of different social groups and different geographical areas can be shown in different periods and based on that, effective interventions can be designed. This study is carried out through a main workshop and expert panels and final consensus on selected indicators. The first draft of indicators and inequity stratifying variables were prepared and then revised by working groups consisting of experts inside and outside Health system. Finally ideas were accepted or rejected after presenting enough reasons and deep examination through the Consensus-Oriented Decision-Making (COMD) model. Fifty two indicators have been determined as health equity indicators in five areas including health, social and human development, economic development, physical environment and infrastructure and governance. Furthermore, for each indicator the proper and practical stratifying variables of inequity were identified. By calculating such indicators, it becomes possible to determine differences in health status of different social groups and different geographical areas.

Human cystic echinococcosis in Yasuj District in Southwest of Iran: an epidemiological study of seroprevalence and surgical cases over a ten-year period.

Cystic echinococcosis is a zoonotic infection of humans and domestic animals caused by the larval stages of the cestode Echinococcus granulosus. Cystic echinococcosis is one of the most important zoonotic diseases in Iran, where human cases are frequently reported from different regions of the country. The objective of this study was to determine the sero-epidemiological and surgical cases of human hydatidosis in the Yasuj district, a region in southwest of Iran. Serum samples were taken from 500 individuals attending Yasuj health centers. Anti-hydatid cyst antibody was checked by enzyme-linked immunosorbent assay (ELISA), using antigen B. Moreover, retrospective studies were carried out using local hospital records of CE patients between 1997 and 2006. Results of the sero-epidemiological study showed that 36 out of 500 cases (7.2%) have antibody against hydatid cyst. Of these 36 cases, 49.6% were women and 50.4% were men. The highest rate of infection was recorded in individuals aged between 30 and 39 years. Hospital records showed that during the 10 years, 105 cases of hydatidosis were admitted in Yasuj hospitals. Of all cases, 70 (66.7%) were women and 35 (33.3%) were men. Hepatic cyst was recorded in 81% of the cases where nephrotic cysts were the second most prevalent ones. Recurrence of the disease was noted in 14.3% of all cases. Results of this study demonstrated that hydatidosis is an important endemic disease, with a nearly constant prevalence rate during the last 10 years, in Yasuj district in Iran. Further studies are needed to investigate the reasons for high rate of surgical cases in housewives and striking prevalence of hydatidosis in a specific (30-40 years) age group.