Immunoglobulins assessment (IgE,G,A,M) in some Iraqi patients with acute and chronic urticaria

60 patients diagnosed as having urticaria were included in the study ; 30 patients were effected with acute urticaria and 30 patients were affected with chronic urticaria. In addition, 30 healthy adult volunteers were selected as control group .The patients and control groups sera were examined with enzyme linked immunosorbent assay ( ELISA) to detect total level IgE and radial immunodiffusion (RID) to detect levels of IgG , IgA and IgM . The total level of IgE in acute urticaria ( 1.45±0.13) IU/mL and chronic urticaria (2.12 ± 0.10) IU/mL patients were significantly higher than the control groups ( 0.85 ± 0.10)IU/mL (

PREVALENCE OF CONSANGUINEOUS MARRIAGES IN SOUTH SINAI, EGYPT

A total of 3961 married couples from six major geographical areas representing the South Sinai governorates in Egypt were studied to assess the rate of consanguineous marriage. The population of six selected areas (St Catherines, Nuweiba, Abu Rudeis, Ras Sudr, El Tor and Abu Zenima) were subdivided into Bedouin, urban and mixed populations. A questionnaire-based interview was conducted showing that the consanguinity rate in this region is 37.5%, with the highest rate recorded in Abu Rudeis (52.3%) and lowest rate in Nuweiba (24.1%). Consanguinity was significantly higher among the Bedouin population compared with the urban population in Abu Rudeis, Ras Sudr, El Tor and Abu Zenima, while in St Catherines and Nuweiba there was no statistically significant difference. Among consanguineous couples, 5%, 60% and 35% were double first cousins, first cousins and second cousins respectively. The mean inbreeding coefficient α of the studied population was 0.0184

Rare single gene disorders: estimating baseline prevalence and outcomes worldwide

As child mortality rates overall are decreasing, non-communicable conditions, such as genetic disorders, constitute an increasing proportion of child mortality, morbidity and disability. To date, policy and public health programmes have focused on common genetic disorders. Rare single gene disorders are an important source of morbidity and premature mortality for affected families. When considered collectively, they account for an important public health burden, which is frequently under-recognised. To document the collective frequency and health burden of rare single gene disorders, it is necessary to aggregate them into large manageable groupings and take account of their family implications, effective interventions and service needs. Here, we present an approach to estimate the burden of these conditions up to 5 years of age in settings without empirical data. This approaches uses population-level demographic data, combined with assumptions based on empirical data from settings with data available, to provide population-level estimates which programmes and policy-makers when planning services can use

Methods to estimate access to care and the effect of interventions on the outcomes of congenital disorders

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of Congenital Disorders (MGDb) seeks to meet this need by combining general biological principles with observational and demographic data, to generate estimates of the burden of congenital disorders. A range of interventions along the life course can modify adverse outcomes associated with congenital disorders. Hence, access to and quality of services available for the prevention and care of congenital disorders affects both their birth prevalence and the outcomes for affected individuals. Information on this is therefore important to enable burden estimates for settings with limited observational data, but is lacking from many settings. This paper, the third in this special issue on methods used in the MGDb for estimating the global burden of congenital disorders, describes key interventions that impact on outcomes of congenital disorders and methods used to estimate their coverage where empirical data are not available

"I am your mother and your father!": In vitro derived gametes and the ethics of solo reproduction

In this paper, we will discuss the prospect of human reproduction achieved with gametes originating from only one person. According to statements by a minority of scientists working on the generation of gametes in vitro, it may become possible to create eggs from men’s non-reproductive cells and sperm from women’s. This would enable, at least in principle, the creation of an embryo from cells obtained from only one individual: ‘solo reproduction’. We will consider what might motivate people to reproduce in this way, and the implications that solo reproduction might have for ethics and policy. We suggest that such an innovation is unlikely to revolutionise reproduction and parenting. Indeed, in some respects it is less revolutionary than in vitro fertilisation as a whole. Furthermore, we show that solo reproduction with in vitro created gametes is not necessarily any more ethically problematic than gamete donation—and probably less so. Where appropriate, we draw parallels with the debate surrounding reproductive cloning. We note that solo reproduction may serve to perpetuate reductive geneticised accounts of reproduction, and that this may indeed be ethically questionable. However, in this it is not unique among other technologies of assisted reproduction, many of which focus on genetic transmission. It is for this reason that a ban on solo reproduction might be inconsistent with continuing to permit other kinds of reproduction that also bear the potential to strengthen attachment to a geneticised account of reproduction. Our claim is that there are at least as good reasons to pursue research towards enabling solo reproduction, and eventually to introduce solo reproduction as an option for fertility treatment, as there are to do so for other infertility related purposes

Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations

Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population

Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation

Consanguinity and reproductive health among Arabs

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity

Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function

Next‐generation sequencing (NGS) has been instrumental in solving the genetic basis of rare inherited diseases, especially neurodevelopmental syndromes. However, functional workup is essential for precise phenotype definition and to understand the underlying disease mechanisms. Using whole exome (WES) and whole genome sequencing (WGS) in four independent families with hypotonia, neurodevelopmental delay, facial dysmorphism, loss of white matter, and thinning of the corpus callosum, we identified four previously unreported homozygous truncating PPP1R21 alleles: c.347delT p.(Ile116Lysfs*25), c.2170_2171insGGTA p.(Ile724Argfs*8), c.1607dupT p.(Leu536Phefs*7), c.2063delA p.(Lys688Serfs*26) and found that PPP1R21 was absent in fibroblasts of an affected individual, supporting the allele's loss of function effect. PPP1R21 function had not been studied except that a large scale affinity proteomics approach suggested an interaction with PIBF1 defective in Joubert syndrome. Our co‐immunoprecipitation studies did not confirm this but in contrast defined the localization of PPP1R21 to the early endosome. Consistent with the subcellular expression pattern and the clinical phenotype exhibiting features of storage diseases, we found patient fibroblasts exhibited a delay in clearance of transferrin‐488 while uptake was normal. In summary, we delineate a novel neurodevelopmental syndrome caused by biallelic PPP1R21 loss of function variants, and suggest a role of PPP1R21 within the endosomal sorting process or endosome maturation pathway