Prevalence Of Congenital Disease Research Articles

P-720 Frequency of recessive genetic mutations in gamete donation program participants

Abstract Study question Is it possible to determine which are the most prevalent genetic diseases in our argentinian gamete donor population to develop a regional genetic panel and carry out correct pre-reproductive counseling? Summary answer We found the most frequent recessive genetic diseases in the gamete donor population, and determined the frequency of positives and negatives for all analyzed mutations. What is known already The access of the population with fertility problems to the gamete donation program is every day more frequent. The analysis of recessive genetic mutations of both recipients and gamete donors is essential to ensure the absence of some diseases in the offspring. There are different ways to study the carrier of monogenic diseases, one of them is the CGT® (CARRIER GENETIC TEST), which could be performed on individuals with no previous personal or family history of disease in order to have knowledge of the asymptomatic carrier status and to reduces the incidence of genetic abnormalities. Study design, size, duration Retrospective descriptive study. 586 blood samples obtained in Nascentis (Cordoba) from December 2016 to November 2019 were analyzed. Of these, 159 were from donors who belonged to the gamete donation program. Participants/materials, setting, methods CGT® results of 159 donors of both sexes were analyzed. A blood sample was drawn from each patient and the kit was sent to Igenomix® for the corresponding CGT® analysis. A complete list of mutations was obtained, the most frequent were identified and the frequency of each one was calculated. We also created the ranking of the fifteen most frequent mutations in the population of oocyte and sperm donors. Main results and the role of chance The 159 CGT® analysis allowed us to compile a list of a total of 63 diseases present in the sample. 78.3% of the donors presented one or more mutations. 69.4% of women and 78.5% of men were positive for at least one mutation. Among men, the most frequent mutation was phenylketonuria (18.1%). Among women, the most frequent were Usher syndrome (8%), Oculocutaneous albinism type 2, Glycine encephalopathy and cystic fibrosis (5%). Other frequent ones were Wilson's disease, central core congenital myopathy, and retinitis pigmentosa. Limitations, reasons for caution It is possible that an increase in the number of CGT® analyzed slightly modifies some of the positions in the ranking of diseases, so it is suggested to carry out studies with a larger sample size in order to obtain more comprehensive conclusions. Wider implications of the findings The analysis of recessive genetic mutations of the gamete donors represents a fundamental tool to avoid the appearance of diseases in the offspring. Each fertility center should know the frequency of occurrence of the most common and/or serious diseases in order to obtain safer results in each of their treatments. Trial registration number not applicable

Hyperlipidemia in Children and Adolescents.

While coronary artery disease (CAD) is thought to be a disease of adulthood, atherosclerosis can originate in childhood and adolescence. There is a paucity of randomized controlled treatment trials regarding dyslipidemia among the younger population. However, it is apparent that childhood dyslipidemia is associated with an earlier onset of CAD. Most recent guidelines by the American College of Cardiology (ACC) and American Heart Association (AHA) focus on lifestyle modification and lifetime risk of atherosclerotic disease, as well as adequate screening measures. Genetic factors, environmental contributors such as pollution, obesity linked to poor nutrition, and sedentary lifestyles are shown to be associated with increased lipid levels and early CAD among children and adolescents. Familial hyperlipidemia is one of the most prevalent genetic diseases and can affect 1 in 250 individuals. A multimodal treatment plan is most effective for children and adolescents with dyslipidemia including lifestyle changes (a modified diet and moderate physical activity) and pharmacologic intervention. The mainstay of pharmacologic treatment for childhood dyslipidemia is similar to that of adults. Statins are the most widely used medications. Newer medications have proven integral in treatment for genetic dyslipidemias including evolocumab and evinacumab.

Genomics in Egypt: Current Status and Future Aspects.

Egypt is the third most densely inhabited African country. Due to the economic burden and healthcare costs of overpopulation, genomic and genetic testing is a huge challenge. However, in the era of precision medicine, Egypt is taking a shift in approach from “one-size-fits all” to more personalized healthcare via advancing the practice of medical genetics and genomics across the country. This shift necessitates concrete knowledge of the Egyptian genome and related diseases to direct effective preventive, diagnostic and counseling services of prevalent genetic diseases in Egypt. Understanding disease molecular mechanisms will enhance the capacity for personalized interventions. From this perspective, we highlight research efforts and available services for rare genetic diseases, communicable diseases including the coronavirus 2019 disease (COVID19), and cancer. The current state of genetic services in Egypt including availability and access to genetic services is described. Drivers for applying genomics in Egypt are illustrated with a SWOT analysis of the current genetic/genomic services. Barriers to genetic service development in Egypt, whether economic, geographic, cultural or educational are discussed as well. The sensitive topic of communicating genomic results and its ethical considerations is also tackled. To understand disease pathogenesis, much can be gained through the advancement and integration of genomic technologies via clinical applications and research efforts in Egypt. Three main pillars of multidisciplinary collaboration for advancing genomics in Egypt are envisaged: resources, infrastructure and training. Finally, we highlight the recent national plan to establish a genome center that will aim to prepare a map of the Egyptian human genome to discover and accurately determine the genetic characteristics of various diseases. The Reference Genome Project for Egyptians and Ancient Egyptians will initialize a new genomics era in Egypt. We propose a multidisciplinary governance system in Egypt to support genomic medicine research efforts and integrate into the healthcare system whilst ensuring ethical conduct of data.

Establishment and Characterization of MUi027-A: A Novel Patient-Derived Cell Line of Polycystic Kidney Disease with PKD1 Mutation.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent genetic diseases affecting the kidneys. A genetically specific mutation model is required to comprehend its pathophysiology and to develop a drug treatment. In this study, we successfully developed human induced pluripotent stem cells (hiPSCs) named MUi027-A from skin fibroblasts of a patient diagnosed with ADPKD and carrying the PKD1 frameshift mutation (c.7946_7947delCT). MUi027-A cells showed the same genetic fingerprints as the parental cells, including the presence of the PKD1 mutation. MUi027-A hiPSCs displayed embryonic stem cell-like characteristics with the capability of differentiating into the three germ layers. Upon directed differentiation, MUi027-A hiPSCs could be differentiated into tubular organoids with the expression of renal cell markers. Furthermore, we compared the efficiency of cyst formation in two human iPSC lines with different PKD1 mutations. When cyst formation was induced by either forskolin or blebbistatin, MUi027-A hiPSC-derived kidney organoids displayed higher frequencies of cyst formation when compared to organoids generated from an iPSC cell line with non-truncating PKD1 mutation genotype (c.5878C > T), suggesting the presence of physiological differences in the mechanism of cyst formation between different PKD1 mutants. Overall, we generated and characterized a novel human iPSC line with a specific PKD mutation and demonstrated its potential as a disease model to study the pathophysiology of genetic determinants in the development of ADPKD disease.

Precise in vivo functional analysis of DNA variants with base editing using ACEofBASEs target prediction.

Single nucleotide variants (SNVs) are prevalent genetic factors shaping individual trait profiles and disease susceptibility. The recent development and optimizations of base editors, rubber and pencil genome editing tools now promise to enable direct functional assessment of SNVs in model organisms. However, the lack of bioinformatic tools aiding target prediction limits the application of base editing in vivo. Here, we provide a framework for adenine and cytosine base editing in medaka (Oryzias latipes) and zebrafish (Danio rerio), ideal for scalable validation studies. We developed an online base editing tool ACEofBASEs (a careful evaluation of base-edits), to facilitate decision-making by streamlining sgRNA design and performing off-target evaluation. We used state-of-the-art adenine (ABE) and cytosine base editors (CBE) in medaka and zebrafish to edit eye pigmentation genes and transgenic GFP function with high efficiencies. Base editing in the genes encoding troponin T and the potassium channel ERG faithfully recreated known cardiac phenotypes. Deep-sequencing of alleles revealed the abundance of intended edits in comparison to low levels of insertion or deletion (indel) events for ABE8e and evoBE4max. We finally validated missense mutations in novel candidate genes of congenital heart disease (CHD) dapk3, ube2b, usp44, and ptpn11 in F0 and F1 for a subset of these target genes with genotype-phenotype correlation. This base editing framework applies to a wide range of SNV-susceptible traits accessible in fish, facilitating straight-forward candidate validation and prioritization for detailed mechanistic downstream studies.

Rehabilitation of congenitally missing teeth with precision attachment and fixed PFM bridge: Case reports

The definition of hypodontia is obvious and unambiguous: “one or additional congenitally absent teeth” it’s a genetic disease that denotes a stronger clinical expression of hypodontia, includes a wide and non-specific. To define oligodontia. The “absence of the many teeth, sometimes related to little size of the prevailing teeth and alternative anomalies”. The prevalence of genetic disease has been reported as zero.3%. It affects females the maximum amount as males, with a gender quantitative relation of 3:2.3. Genes accountable for non syndromic genetic disease area unit found to be MSX1 and PAX9 genes. Within the current edition of the glossary of dentistry Terms, the definition reads “the formation of less than full complete teeth. Several such teeth area unit smaller than normal”. Current article describe a case of genetic disease treated with jaw unilateral exactitude attachment on distal side of 11 and bar & clip maintained overdenture for the second quadrant with a 1 piece forged denture support of anterioposterior-palatal strap and mandibular complete arch rehabilitation with metal ceramic crowns.

Comparison of Immunoglobulins Status In Splenectomized And Non-Splenectomized Patients With Major Beta-Thalassemia

Background: Thalassemia is one of the most prevalent genetic disorders globally, and infections are one of the major causes of death in these patients. Various studies have attributed the increased susceptibility to bacterial infections in thalassemia patients to changes in their immunological status. Objectives: This research aimed to measure serum levels of immunoglobulins (Igs) in Thalassemia Major (TM) patients and in the control group. Methods: The study included forty TM patients (20 splenectomized and 20 non-splenectomized) and 20 healthy participants (the control group). Three groups were matched for age and gender. Mean serum levels of immunoglobulins (IgG, IgA and IgM) were measured for all individuals by ELISA. P<0.05 was considered the significance level. Results: Increased serum IgG and IgA levels and significantly reduced serum IgM levels were observed in the splenectomized patients compared to the non-splenectomized ones. A comparison of the study groups revealed that serum IgG and IgA levels in the splenectomized patients and the mean serum IgM and IgG levels in the non-splenectomized patients were higher than those of the healthy participants. The mean serum IgM levels in the splenectomized patients and the mean serum IgG levels in the non-splenectomized patients were lower than those of the control group. Conclusions: The results showed that splenectomy could change the immunological status of thalassemia patients. Nevertheless, the exact mechanism for this change was not clear. Studying the serum levels of immunoglobulins might be useful in determining the severity of infections in TM patients.

EPIDEMIOLOGY OF DOWN’S SYNDROME & Β- THALASSEMIA IN INDIA

Down’s syndrome and Beta (β) Thalassemia are commonly prevalent genetic diseases worldwide. Down’s syndrome is predominantly caused by an extra copy of chromosome 21 or trisomy 21. Maternal age above 35 years significantly increases the chances of a Down’s syndrome birth. In India, there are approximately 21,000 Down’s syndrome births every year. β-Thalassemia is a blood disorder caused by abnormal synthesis of the β chains of hemoglobin. India has over 35-45 million carriers of this disease. This is a survey-based study, which aims to understand the epidemiology of Down’s syndrome and Beta Thalassemia in the Indian population. This online survey was answered by 297 Indian or Indian origin adults. Both females and males were the respondents. Results of the study indicated that prevalence of Down’s syndrome is low in India while that of β-thalassemia is moderate. The correlation between the maternal and paternal ages at the time of birth of a Downs syndrome affected person was determined and the analyses showed that there was a positive correlation.

What is The Prevalence of Genetic Disorders That Cause Effects On In Fertility?

Infertility rates increases day by day and major reason can be genetic disorders.Objective: To review the prevalence and effects of genetic defects that can cause infertility.10 to 20% of patients have severe infertility disorders. To find out whether genetic material defects are really major infertility cause or not? And what are their prevalence.. Infertility is common health condition. Genetic cause are majorly unexplained but 2300 genes expressed that can retranslate and their mutation can cause of infertility.Handfull of genes and genetic effects are associated with human genome to express genes. Mostly tests added to check male infertility annually.Methods: I analyse and evaluate 12 articles from (1997-2011) from Google scholar, PubMed etc. All data is reviewed from infertility complaints. The data is extracted from Medline, PubMed and Obsgyne online library.Results: Those studies which conducted between years 1985 to 2011 are included in review. The sample size included more than 300 men and women aged between 20 to 40 years. In this study we evaluated that genomic technologies and advent of fertility tips can help in fertile patients. Metabolic chromosomal defects can be genetic disorders by deletion of chromosomes abnormLly.SOX9 chromosome is also play basic role in men fertility. Semen collection and measurements done and proper advances can be seen through research to follow up infertile patients. Comprehensive diagnosis started to advance the research and to increase the prognostic information.Conclusions: Infertility can be caused by genomic abnormalities and chromosomal abnormalities. Molecular techniques can help to reduce the abnormalities. In reality we are unable to establish genotype phenotype relationship and various testicular pattern to see infertile men.

Web-Based Tool (FH Family Share) to Increase Uptake of Cascade Testing for Familial Hypercholesterolemia: Development and Evaluation.

BackgroundFamilial hypercholesterolemia, a prevalent genetic disorder, remains significantly underdiagnosed in the United States. Cascade testing, wherein individuals diagnosed with familial hypercholesterolemia— probands—contact their family members to inform them of their risk for familial hypercholesterolemia, has low uptake in the United States. Digital tools are needed to facilitate communication between familial hypercholesterolemia probands and their family members and to promote sharing of familial hypercholesterolemia–related risk information.ObjectiveWe aimed to create and evaluate a web-based tool designed to enhance familial communication and promote cascade testing for familial hypercholesterolemia.MethodsA hybrid type 1 implementation science framework and a user-centered design process were used to develop an interactive web-based tool—FH Family Share—that enables familial hypercholesterolemia probands to communicate information about their familial hypercholesterolemia diagnosis with at-risk relatives. Probands can also use the tool to draw a family pedigree and learn more about familial hypercholesterolemia through education modules and curated knowledge resources. Usability guidelines and standards were taken into account during the design and development of the tool. The initial prototype underwent a cognitive walkthrough, which was followed by usability testing with key stakeholders including genetic counselors and patients with familial hypercholesterolemia. Participants navigated the prototype using the think-aloud technique, and their feedback was used to refine features of the tool.ResultsKey themes that emerged from the cognitive walkthrough were design, format, navigation, terminology, instructions, and learnability. Expert feedback from the cognitive walkthrough resulted in a rebuild of the web-based tool to align it with institutional standards. Usability testing with genetic counselors and patients with familial hypercholesterolemia provided insights on user experience, satisfaction and interface design and highlighted specific modifications that were made to refine the features of FH Family Share. Genetic counselors and patients with familial hypercholesterolemia suggested inclusion of the following features in the web-based tool: (1) a letter-to-family-member email template, (2) education modules, and (3) knowledge resources. Surveys revealed that 6 of 9 (67%) genetic counselors found information within FH Family Share very easy to find, and 5 of 9 (56%) genetic counselors found information very easy to understand; 5 of 9 (56%) patients found information very easy to find within the website, and 7 of 9 (78%) patients found information very easy to understand. All genetic counselors and patients indicated that FH Family Share was a resource worth returning to.ConclusionsFH Family Share facilitates communication between probands and their relatives. Once informed, at-risk family members have the option to seek testing and treatment for familial hypercholesterolemia.

What is the Prevalence of genetic disorders that cause effects on infertility

Infertility rates increases day by day and major reason can be genetic disorders.Objective: To review the prevalence and effects of genetic defects that can cause infertility.10 to 20% of patients have severe infertility disorders. To find out whether genetic material defects are really major infertility cause or not? And what are their prevalence.. Infertility is common health condition. Genetic cause are majorly unexplained but 2300 genes expressed that can retranslate and their mutation can cause of infertility.Handfull of genes and genetic effects are associated with human genome to express genes. Mostly tests added to check male infertility annually.Methods: I analyse and evaluate 12 articles from (1997-2011) from Google scholar, PubMed etc. All data is reviewed from infertility complaints. The data is extracted from Medline, PubMed and Obsgyne online library.Results: Those studies which conducted between years 1985 to 2011 are included in review. The sample size included more than 300 men and women aged between 20 to 40 years. In this study we evaluated that genomic technologies and advent of fertility tips can help in fertile patients. Metabolic chromosomal defects can be genetic disorders by deletion of chromosomes abnormLly.SOX9 chromosome is also play basic role in men fertility. Semen collection and measurements done and proper advances can be seen through research to follow up infertile patients. Comprehensive diagnosis started to advance the research and to increase the prognostic information.Conclusions: Infertility can be caused by genomic abnormalities and chromosomal abnormalities. Molecular techniques can help to reduce the abnormalities. In reality we are unable to establish genotype phenotype relationship and various testicular pattern to see infertile men.

P101: GUT MICROBIOTA IMPACT ON ANGOLAN CHILDREN WITH SICKLE CELL DISEASE

Background: Sickle cell disease (SCD) is one of the most prevalent genetic diseases, affecting between 20 and 25 million people worldwide. In the Sub-Saharan Africa, where it is more prevalent, it contributes to 50–80% of under-5 mortality. Clinical manifestations of SCD are very heterogeneous and the intestinal microbiome appears to be crucial in the modulation of inflammation, cell adhesion and induction of aged neutrophils, which are the main interveners of recurrent vaso-occlusive crisis. Enterocyte injury, increased permeability, altered microbial composition, and bacterial overgrowth have all been documented as microbial and pathophysiologic changes in the gut microbiome of SCD patients in recent research studies. Microbiota analysis in SCD populations will be essential to demonstrate the importance of specific bacteria and their function in this disease and provide new insights for attenuating symptoms and new drug targets. Aims: Given this, our aim is to sequence by NGS bacterial 16S RNA gene in order to characterize the gut microbiome of SCD children and healthy siblings, as a control. A written informed consent was presented and explained to all the guardian participants prior to the data collection. A total of 72 stool samples were obtained from children between 3–14 years old. Results: Our preliminary results showed that the SCD and control samples exhibit some notable differences in microbiota relative abundance, at different levels of classification. Children with the disease have a higher number of the phylum Actinobacteria (p=0.013) with a mean of sequences of 5.47% (± 3.49), while the siblings have a mean of 3.25% (± 2.98). As for the genus level, only Clostridium cluster XI bacteria was more prevalent in the SCD children, whereas the siblings had higher numbers of Blautia, Aestuariispira, Campylobacter, Helicobacter, Polaribacter and Anaerorhabdus. Conclusion: There is still much to learn before fully relying on the therapeutic approaches for gut modulation, which is why more research in this field is crucial to making this a reality. This works as been supported by FCT/Aga Khan (project n°330842553) and FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020) –H&TRC.

PKD1 deficiency induces Bronchiectasis in a porcine ADPKD model

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder, mainly characterized by the development of renal cysts, as well as various extrarenal manifestations. Previous studies have shown that ADPKD is related to bronchiectasis, while its pathogenic mechanism is unclear. In previous studies, we have generated the PKD1+/− pigs to simulate the progression of cyst formation and physiological alterations similar to those seen in ADPKD patients.MethodsPhenotypic changes to airway epithelial cell and mesenchymal cell in PKD1+/− pigs were assessed by histological analysis. The molecular mechanisms driving these processes were investigated by using PKD1+/− pig lungs, human mesenchymal cells, and generating PKD1 deficient human epithelial cells.ResultsWe identified bronchiectasis in PKD1+/− pigs, which is consistent with the clinical symptoms in ADPKD patients. The deficiency of PKD1 suppressed E-cadherin expression in the airway epithelial barrier, which aggravated invasion and leaded to a perpetuated inflammatory response. During this process, extracellular matrix (ECM) components were altered, which contributed to airway smooth muscle cell phenotype switch from a contractile phenotype to a proliferative phenotype. The effects on smooth muscle cells resulted in airway remodeling and establishment of bronchiectasis.ConclusionTo our knowledge, the PKD1+/− pig provides the first model recapitulating the pathogenesis of bronchiectasis in ADPKD. The role of PKD1 in airway epithelial suggests a potential target for development of new strategies for the diagnosis and treatment of bronchiectasis.

A Brief Narrative Review of Glucose 6-phosphate Dehydrogenase Deficiency in Children and Its Genetic Variants

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent enzyme deficiency which leading to substantial morbidity and mortality in children. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme present in cytoplasm, coded by X-linked gene. G6PD catalyzes the initial step in hexose monophosphate shunt, which is a rate limiting reaction. This shunt helps in producing NADPH (Nicotinamide adenine dinucleotide phosphate), a reducing equivalent that helps glutathione reductase to regenerate reduced glutathione (GSH). Due to its crucial role in defence against oxidizing species, it is perceived that any mutation in G6PD encoding gene can affect enzyme’s structural and functional integrity leading to malfunctioning of enzyme. G6PD deficiency is a highly prevalent genetic disorder which is transmitted as X–linked recessive pattern. Nearly 210 variants have been reported all over the world. In India, G6PD deficiency is a significant public health problem. It is an important cause for drug induced hemolysis in children. G6PD gene variants are often named as per the geographical area where they were first discovered. In India Mediterranean, Orissa, Jammu, Andhra Pradesh, Kalyan-Kerala and G6PD West Bengal are frequently seen. G6PD Mediterranean leads to severe deficiency when compared to others. Worldwide highest preponderance of g6PD deficiency is seen in African sub Saharan region and Arabian Peninsula.

Characterization of Structural Hemoglobin Variants by Top-Down Mass Spectrometry and R Programming Tools for Rapid Identification.

Hemoglobinopathies are one of the most prevalent genetic disorders, affecting millions throughout the world. These are caused by pathogenic variants in genes that control the production of hemoglobin (Hb) subunits. As the number of known Hb variants has increased, it has become more challenging to obtain unambiguous results from routine chromatographic assays employed in the clinical laboratory. Top-down proteomic analysis of Hb by mass spectrometry is a definitive method to directly characterize the sequences of intact subunits. Here, we apply "chimeric ion loading" to characterize Hb β subunit variants. In this technique, product ions derived from complementary dissociation techniques are accumulated in a multipole storage device before delivery to a 21 T Fourier-transform ion cyclotron resonance mass spectrometer for simultaneous detection. To further improve the efficiency of identification of Hb variants and localization of the mutation site(s), we developed an R programming script, "Variants Identifier", to search top-down data against a database containing accurate intact mass differences and diagnostic ions from investigated Hb variants. A second R script, "PredictDiag", was developed and employed to determine relevant diagnostic ions for additional Hb variants with known sequences. These two R scripts were successfully applied to the identification of a Hb δ-β fusion protein and other Hb variants. The combination of chimeric ion loading and the above R scripts enables rapid and reliable interpretation of top-down mass spectrometry data, regardless of activation type, for Hb variant identification.

Health promotion practices and coping behaviors among caregivers of children suffering from thalassemia major

According to the Global Health Organisation thalassemia is the most prevalent genetic disorder which immensely affect the life of about 100,000 infants in over 60 countries. In India, thalassemia major is also the most prevalent genetic disorder. As indicated by the national statistics report, 22,000 patients of thalassemia major exist in our country. Thalassemia major is a chronic disease which has a long treatment regimen thus putting the affected children and their caregivers through a variety of challenges both physically and mentally. To assess the health promotion practices and coping behaviors among parents/caregivers of children suffering from Thalassemia Major.A descriptive study was conducted in the thalassemia clinic, APC, PGIMER, Chandigarh. Data was collected from 70 parents of thalassemic children with age group of 4 to 17 years on Socio Demographic Profile, clinical profile, Coping Health Inventory of Parents (CHIP) and Health Promotion Practices (HPP). The study showed that 51.9% caregivers of thalassemic children reported that they considered the items enlisted in CHIP to be moderately helpful, 45.2% reported them to be extremely helpful while according to 2.9% of the subjects, they were minimally helpful. All the subjects were in the “always” level of the HPP i.e. caregivers were following health promotion practices. This study also revealed that majority of parents (61%) did not receive any genetic counselling during their first pregnancy. The study concluded the association between major study variables like Health Promotion practices (HPP) and Coping Health Inventory Of Parents (CHIP) analysed by Pearson correlation. The results revealed that there was low positive correlation between HPP and CHIP i.e. +0.078.

Prevalence of Glucose-6-phosphate Dehydrogenase Deficiency in Aligarh, India: A Pilot Study

Introduction: Deficiency of glucose-6-phosphate dehydrogenase (G6PD) enzyme in erythrocytes is among the prevalent X-linked recessive genetic disorders and affects approximately 400 million people across the globe. It causes neonatal hyperbilirubinemia, also hemolysis eventually leading to hemolytic anemia when exposed to oxidative stress. Purpose: The purpose of the study was to find out the prevalence of G6PD deficiency in Aligarh (Western Uttar Pradesh) India. Materials and Methods: The data and samples were collected from a total of 106 individuals. All the required information were recorded in a standardized questionnaire, blood was taken with their prior consent. Blood typing test and fluorescent spot test (FST) were performed, spots were arranged accordingly and observed. Results: Out of total 106 individuals surveyed, 10% of them were found to be deficient for G6PD enzyme, 5% were intermediate, and 85% were normal. Significant association was found for G6PD deficiency and gender (P < 0.05) of the individuals while non-significant association were reported for G6PD deficiency and consanguinity (P < 0.8) and for G6PD deficiency and blood groups (P < 0.9). Conclusion: FST is a good method for G6PD screening and detecting the deficiency in fields. This pilot study highlights the prevalence of G6PD enzymopathy in Aligarh and will help government programs of this area to prevent and control the genetic disorder

Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study

Neonates with genetic disorders or congenital anomalies (CA) contribute considerably to morbidity and mortality in neonatal intensive care units (NICUs). The objective of this study is to study the prevalence of genetic disorders in an academic level IV NICU. We retrospective collected and analyzed both clinical and genetic data of all 1444 infants admitted to the NICU of the Radboudumc (October 2013 to October 2015). Data were collected until infants reached at least 2 years of age. A total of 13% (194/1444) of the patients were genetically tested, and 32% (461/1444) had a CA. A total of 37% (72/194) had a laboratory-confirmed genetic diagnosis. In 53%, the diagnosis was made post-neonatally (median age = 209 days) using assays including exome sequencing. Exactly 63% (291/461) of the patients with CA, however, never received genetic testing, despite being clinically similar those who did.Conclusions: Genetic disorders were suspected in 13% of the cohort, but only confirmed in 5%. Most received their genetic diagnosis in the post-neonatal period. Extrapolation of the diagnostic yield suggests that up to 6% of our cohort may have remained genetically undiagnosed. Our data show the need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.What is Known:• Genetic disorders are suspected in many neonates but only genetically confirmed in a minority.• The presence of a genetic disorder can be easily missed and will often lead to a diagnostic odyssey requiring extensive evaluations, both clinically and genetically.What is New:• Different aspects of the clinical features and uptake of genetic test in a NICU cohort.• The need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.

Investigating the reasons for marriage among couples with thalassemia minor, in Iran.

Thalassemia is one of the most prevalent genetic disorders in Iran. The birth of a child with thalassemia major is associated with many problems for the family, and society. In the present study, the reasons for marriage among people with thalassemia minor in Iran, in spite of receiving medical advice against it, have been investigated. The present study was a qualitative content analysis conducted in 2019 with the participation of 12 couples (24 participants) with thalassemia minor living in Rafsanjan, Iran; and 2 counselors working with thalassemia patients. Data collection was conducted through in-depth interviews. All interviews were recorded and transcribed. The text was read several times, categorized and main themes were extracted according to content analysis methods. The present study shows that giving inadequate or inaccurate information to people, strong emotional attachment between couples, taking the test at the wrong time, family interference and family insistence on marriage, having seen cases with no problems, and specific thoughts and beliefs are the most important reasons for marriage among couples with thalassemia minor in Iran. According to the results of the present study, the importance of providing thorough and accurate information to the public, setting an appropriate time for counseling and screening which is not immediately before the marriage ceremony, and briefing more efficiently at the time of counseling can help prevent marriage among couples with thalassemia minor in Iran.

Diagnosis and Management of Hematological Manifestations of Gaucher Disease

Gaucher disease (GD) is a lysosomal storage disorder that occurs due to an inherited inborn error of metabolism. GD manifested due to the deficient activity of the glucocerebrosidase enzyme that results in the accumulation of the harmful glucocerebrosides glycolipids in different body cells. There are three main types of GD that differ from each other in their clinical presentations. Type I characterized by the absence of any neurological involvement, unlike Type II and Type III. Patients with Gaucher can be presented with visceral manifestations (including splenomegaly, hepatomegaly, or abdominal pain), hematological manifestation (anemia or thrombocytopenia or bleeding diathesis), bone manifestations (painful limbs or pathological fractures), or neurological manifestations (including neck rigidity, swallowing disorder, or oculomotor paralysis). In the Middle East, especially Saudi Arabia, a higher prevalence of genetic diseases was observed compared to reported rates in Europe and the United States. However, published data on the characteristics and treatment patterns of Gaucher patients in Saudi Arabia are still lacking in the literature. Therefore, the present manuscript aimed to present an overview of the GD situation in Saudi Arabia by bringing together a panel of Saudi hematology experts to share their views on current trends and practices in Saudi Arabia regarding GD. The experts agreed that there is no available data regarding the prevalence and incidence of GD in Saudi Arabia, therefore the experts recommend establishing a national registry for Gaucher cases. The diagnosis of GD is challenging as the disease is rare and obscure, even to hematologists. The experts also recommend shifting from the dried blood spots test to genetic testing in the future to confirm the diagnosis of GD. The experts agreed on the need to organize awareness campaigns to familiarize the primary care physicians and junior hematologists about the common presentations and management of GD.