Pathogenic homozygous mutation in the pleckstrin homology domain of RASA1 is responsible for familial tricuspid atresia in an Iranian consanguineous family

Objective: Tricuspid atresia [TA] is a rare life-threatening form of congenital heart defect [CHD]. The genetic mechanisms underlying TA are not clearly understood. According to previous studies, the endocardial cushioning event, as the primary sign of cardiac valvulogenesis, is governed by several overlapping signaling pathways including Ras/ ERK pathway. RASA1, a regulator of cardiovascular development, is involved in this pathway and its haploinsufficiency [due to heterozygous mutations] has been identified as the underlying etiology of the autosomal dominant capillary malformation/arteriovenous malformation [CM/AVM]

Materials and Methods: In this prospective study, we used whole exome sequencing [WES] followed by serial bioinformatics filtering steps for two siblings with TA and early onset CM. Their parents were consanguineous which had a history of recurrent abortions. Patients were carefully assessed to exclude extra-cardiac anomalies

Results: We identified a homozygous RASA1 germline mutation, c.1583A>G [p.Tyr528Cys] in the family. This mutation lies in the pleckstrin homology [PH] domain of the gene. The parents who were heterozygous for this variant displayed CM

Conclusion: This is the first study reporting an adverse phenotypic outcome of a RASA1 homozygous mutation. Here, we propose that the phenotypic consequence of the homozygous RASA1 p.Tyr528Cys mutation is more serious than the heterozygous type. This could be responsible for the TA pathogenesis in our patients. We strongly suggest that parents with CM/AVM should be investigated for RASA1 heterozygous mutations. Prenatal diagnosis and fetal echocardiography should also be carried out in the event of pregnancy in heterozygous parents

novel method for quantification of left ventricular noncompaction using two-dimensional echocardiography in children

Although there are several echocardiographic criteria, there is not yet a general consensus about the diagnosis of left ventricular noncompaction. The current criteria are mostly based on the areas with maximal noncompaction in the heart The echocardiographer may miss this maximal point leading to a misdiagnosis. Accordingly, we suggested a new method to measure the percentage of myocardial noncompaction using two-dimensional echocardiography. In this study, the new method was examined on 4 noncompaction and 26 dilated cardiomyopathies, and 25 normal subjects. The percentage of noncompaction was measured at 3 levels [apical, papillary muscle and mitral valve] and averaged. The mean percentages of myocardial noncompaction were 3.59 +/- 2.27, 8.86 +/- 5.52 and 34.7 +/- 26.1 in the control, dilated cardiomyopathy and noncompaction groups, respectively. A value of 17% or greater could distinguish left ventricular noncompaction from dilated cardiomyopathy with 92% specificity and 100% sensitivity and from normal subjects with 100% specificity and sensitivity. This percentage had a statistically significant association with noncompacted to compacted myocardial thickness ratio [P<0.001]. This method showed good correlations with the existing echocardiographic and magnetic resonance criteria. However, it is not dependent on finding the area of maximal involvement Being comparable to magnetic resonance imaging in accuracy, it is easier to perform and more available

[Review of the thirty years experience of the lslamic Republic of lran on social determinants of health and health equity the future course: roles and orientations of the lslamic gonsultative assembly]

Over three decades of research on social determinants of health suggest unequivocal impact of factors like childhood development, education, employment, housing, entertainment, public transportation, agriculture and social support, on people's health. In the aftermath of the Islamic Revolution, there has been eye-catching progress in the areas of maternal and child health. The key role of the Islamic Consultative Assembly in examining and approving five years development plans of the Islamic Republic is irrefutable. The implementation of national development plans has often contained core determinants of health, in particular in the areas of employment, housing, social support, health services, environment and food security. The support rendered by the Islamic Consultative Assembly to promoting health in the past three decades, spurs further hope for greater strides in terms of health indicators of the country, in accordance with the following strategies: - To draw full support of the Health and Medical Commission of the Islamic Consultative Assembly, to ensure approval and monitoring of health oriented laws and regulations and policies in all 14 commissions of the Assembly; - To negotiate and win the support of all members of the Assembly's fractions, and heads of forums for provincial groups of parliamentarians. to encourage approval of health oriented policies at the Assembly and their implementation within provinces; - To cooperate with the Ministry of interior in promoting the performance of the Provincial Councils on Hearth and Food Security and Islamic Councils at city and village levels, to stimulate participation of all in improving the situation of their immediate environment; - To supervise and provide support to the Ministry of Health and Medical Education in further activating the National council on Health and Food Security; - To lunch a monitoring system at the Research Center of the Islamic Consultative Assembly to oversee indicators related to health equity.

Transcatheter atrial septal defect closure under transthorasic echocardiography in children

Atrial septal defect [ASD] device closure is routinely done under the guide of transesophageal or intracardiac echocardiography which are expensive techniques and not easily affordable in developing countries. Using metallic devices, we attempted 32 ASD device closures under transthoracic echocardiography. Of those, 30 procedures were successful [94%]. In two patients with relatively large ASD we encountered difficulty in positioning the device. These patients were referred for surgical closure. ASD device closure can be carried out successfully in most patients under transthoracic echocardiography in situations where transesophageal or intravenous echocardiographies are not available or affordable