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Cancer is a major health concern and accounts for one of the main causes of death worldwide. Innovative strategies are needed to aid in the diagnosis and treatment of different types of cancers. Recently, there has been an evolving interest in utilizing nanobodies of camel origin as therapeutic tools against cancer. Nanotechnology uses nanobodies an emerging attractive field that provides promises to researchers in advancing different scientific sectors including medicine and oncology. Nanobodies are characteristically small-sized biologics featured with the ability for deep tissue penetration and dissemination and harbour high stability at high pH and temperatures. The current review highlights the potential use of nanobodies that are naturally secreted in camels' biological fluids, both milk and urine, in the development of nanotechnology-based therapy for treating different typesQuery of cancers and other diseases. Moreover, the role of nano proteomics in the invention of novel therapeutic agents specifically used for cancer intervention is also illustrated.
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Sick sinus syndrome (SSS) is a group of disorders characterized by an abnormal cardiac impulse formation or propagation from the sinoatrial node. Mutated SCN5A has been reported in SSS, however, homozygosity of SCN5A is exceedingly rare. Here, we report a consanguineous family with four affected children with SSS. Symptomatic bradycardia necessitated implanting a pacemaker in all of them. Sequencing SCN5A revealed a novel homozygous variant (p.Cys1850Arg), which was predicted to interfere with protein folding. Our report describes the phenotype of a novel homozygous SCN5A variant and contributes to the compendium of molecular pathology of inherited arrhythmias in consanguineous populations.
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Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Síndrome do Nó Sinusal/genética , Adolescente , Feminino , Homozigoto , Humanos , Lactente , Masculino , Marca-Passo Artificial , Linhagem , Síndrome do Nó Sinusal/terapia , Adulto JovemRESUMO
Hearing loss (HL) is the most common sensory disorder worldwide and genetic factors contribute to approximately half of congenital HL cases. HL is subject to extensive genetic heterogeneity, rendering molecular diagnosis difficult. Mutations of the transmembrane channel-like 1 (TMC1) gene cause hearing defects in humans and mice. The precise function of TMC1 protein in the inner ear is unknown, although it is predicted to be involved in functional maturation of cochlear hair cells. TMC1 mutations result in autosomal recessive (DFNB7/11) and sometimes dominant (DFNA36) nonsyndromic HL. Mutations in TMC1 are responsible for a significant portion of HL, particularly in consanguineous populations. To evaluate the importance of TMC1 mutations in the Saudi population, we used a combination of autozygome-guided candidate gene mutation analysis and targeted next generation sequencing in 366 families with HL previously shown to lack mutations in GJB2. We identified 12 families that carried five causative TMC1 mutations; including three novel (c.362+3A > G; c.758C > T [p.Ser253Phe]; c.1396_1398delACC [p.Asn466del]) and two reported mutations (c.100C > T [p.Arg34Ter]; c.1714G > A [p.Asp572Asn]). Each of the identified recessive mutation was classified as severe, by both age of onset and severity of HL. Similarly, consistent with the previously reported dominant variant p.Asp572Asn, the HL phenotype was progressive. Eight families in our cohort were found to share the pathogenic p.Arg34Ter mutation and linkage disequilibrium was observed between p.Arg34Ter and SNPs investigated. Our results indicate that TMC1 mutations account for about 3.3% (12/366) of Saudi HL cases and that the recurrent TMC1 mutation p.Arg34Ter is likely to be a founder mutation.
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Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Mutação , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Análise Mutacional de DNA , Orelha Interna/metabolismo , Éxons , Saúde da Família , Feminino , Ligação Genética , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Arábia Saudita , Adulto JovemRESUMO
BACKGROUND: Polycystic kidney disease (PKD) is one of the most common genetic renal diseases and may be inherited in an autosomal dominant or autosomal recessive pattern. Pathogenic variants in two major genes, PKD1 and PKD2, and two rarer genes, GANAB and DNAJB11, cause autosomal dominant PKD (ADPKD). Early onset and severe PKD can occur with PKD1 and PKD2 pathogenic variants and such phenotypes may be modified by second alleles inherited in trans. Homozygous or compound heterozygous hypomorphic PKD1 variants may also cause a moderate to severe disease PKD phenotype. METHODS: Targeted renal gene panel followed by Sanger sequencing of PKD1 gene were employed to investigate molecular causes in early onset PKD patients. RESULTS: In this study, we report four consanguineous Saudi Arabian families with early onset PKD which were associated with biallelic variants in PKD1 gene. CONCLUSIONS: Our findings confirm that PKD1 alleles may combine to produce severe paediatric onset PKD mimicking the more severe autosomal recessive ciliopathy syndromes associated with PKD. Screening of parents of such children may also reveal subclinical PKD phenotypes.
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Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Idade de Início , Criança , Simulação por Computador , Consanguinidade , Análise Mutacional de DNA , Feminino , Homozigoto , Humanos , Rim/diagnóstico por imagem , Masculino , Mutação , Rim Policístico Autossômico Dominante/diagnóstico , Arábia Saudita , UltrassonografiaRESUMO
MOTIVATION: High-throughput sequencing platforms are increasingly used to screen patients with genetic disease for pathogenic mutations, but prediction of the effects of mutations remains challenging. Previously we developed SAAPdap (Single Amino Acid Polymorphism Data Analysis Pipeline) and SAAPpred (Single Amino Acid Polymorphism Predictor) that use a combination of rule-based structural measures to predict whether a missense genetic variant is pathogenic. Here we investigate whether the same methodology can be used to develop a differential phenotype predictor, which, once a mutation has been predicted as pathogenic, is able to distinguish between phenotypes-in this case the two major clinical phenotypes (hypertrophic cardiomyopathy, HCM and dilated cardiomyopathy, DCM) associated with mutations in the beta-myosin heavy chain (MYH7) gene product (Myosin-7). RESULTS: A random forest predictor trained on rule-based structural analyses together with structural clustering data gave a Matthews' correlation coefficient (MCC) of 0.53 (accuracy, 75%). A post hoc removal of machine learning models that performed particularly badly, increased the performance (MCC = 0.61, Acc = 79%). This proof of concept suggests that methods used for pathogenicity prediction can be extended for use in differential phenotype prediction. AVAILABILITY AND IMPLEMENTATION: Analyses were implemented in Perl and C and used the Java-based Weka machine learning environment. Please contact the authors for availability. CONTACTS: andrew@bioinf.org.uk or andrew.martin@ucl.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Mutação , Cadeias Pesadas de Miosina , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Análise por Conglomerados , Humanos , Miosinas VentricularesRESUMO
BACKGROUND: Understanding and predicting the effects of mutations on protein structure and phenotype is an increasingly important area. Genes for many genetically linked diseases are now routinely sequenced in the clinic. Previously we focused on understanding the structural effects of mutations, creating the SAAPdb resource. RESULTS: We have updated SAAPdb to include 41% more SNPs and 36% more PDs. Introducing a hydrophobic residue on the surface, or a hydrophilic residue in the core, no longer shows significant differences between SNPs and PDs. We have improved some of the analyses significantly enhancing the analysis of clashes and of mutations to-proline and from-glycine. A new web interface has been developed allowing users to analyze their own mutations. Finally we have developed a machine learning method which gives a cross-validated accuracy of 0.846, considerably out-performing well known methods including SIFT and PolyPhen2 which give accuracies between 0.690 and 0.785. CONCLUSIONS: We have updated SAAPdb and improved its analyses, but with the increasing rate with which mutation data are generated, we have created a new analysis pipeline and web interface. Results of machine learning using the structural analysis results to predict pathogenicity considerably outperform other methods.
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Biologia Computacional/métodos , Doenças Genéticas Inatas/genética , Mutação/genética , Fenótipo , Conformação Proteica , Proteínas/genética , Software , Substituição de Aminoácidos/genética , Inteligência Artificial , Humanos , Internet , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Establishing a national screening program for hemophilia patients is highly encouraged by the World Health Organization and the World Federation of Hemophilia. Hence, this study aimed to analyze the variant spectrum of F8 and F9 genes in Arab hemophilia patients. Molecular genetic and sequencing studies were performed on a cohort of 135 Saudi hemophilia patients. Out of all screened hemophilia patients (97 hemophilia A and 39 hemophilia B), 15 (11.1%) were positive for inversion 22 and 4 (3%) for inversion 1. Out of a total of 32 (23.7%) substitution/deletion mutations, 2 novel variants were identified: a novel splice acceptor site missense mutation (c.5816-2A > G) causing a pathogenic variant of the F8 gene and another splicing site point mutation in intron/exon 23 (g.164496G > A). The frequent F8 variants were (c.409A > C, p.T137P) in exon 4, (c.760A > G) in exon 6, and (c.1835G > C, p.R612P) in exon 12, while the frequent F9 variants were (c.580A > G) in exon 6 and (c.880C > T) in exon 8. These study data will enrich the spectrum of the genetic databases in the Arab population that could be applied in the future for national genetic counseling.
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Hemofilia A , Hemofilia B , Humanos , Hemofilia A/diagnóstico , Hemofilia A/genética , Fator VIII/genética , Hemofilia B/genética , Mutação de Sentido Incorreto , Genótipo , MutaçãoRESUMO
The identification of lipolytic bioactive compounds via the functional stimulation of carbohydrate response element-binding protein-1 (CREBp-1) and AMP-activated protein kinase (AMPK) is most warranted. Nano lipid carriers (NLCs) are currently being considered within drug delivery development as they facilitate controlled drug release and have intracellular bioavailability after encapsulating the active principles with lipid matrix. The present study has been designed to synthesize punicalagin, and ketogenic amino acids (KAA) loaded with organic lipid carriers to optimize the liposome-assisted intracellular delivery's bioavailability. Punicalagin (PUNI) and KAA (tryptophan, methionine, threonine, lysine, and leucine) were encapsulated with chia seed phospholipids by homogenization, emulsification, and cold ultra-sonication method to obtain nano lipid carriers (NLC). The physicochemical characterization of NLCs has been carried out using Zetasizer, FT-IR, and TEM analysis. Punicalagin and ketogenic amino acid-loaded NLCs (NLC-PUNI-KAA) were identified with an average diameter of 240 to 800 nm. The biosafety of NLC-PUNI-KAA has been evaluated in human mesenchymal stem cells. PI staining confirmed that a 0.4, 0.8 or 1.6µg/dL dose of NLC-PUNI-KAA potentially maintains nuclear integration. NLC-PUNI-KAA treated with maturing adipocytes decreased lipid accumulation and significantly increased the gene expression levels of fatty acid beta-oxidation (PPARγC1α, UCP-1 and PRDM-16) pathways when compared to free PUNI (5 µg/dL) treatment. The lipolytic potential has been confirmed by the functional activation of AMPK and CREBp-1 protein levels. In conclusion, NLC-PUNI-KAA treatment effectively increased mitochondrial efficiency more than free punicalagin or orlistat treated maturing adipocyte. Enhanced lipolysis and decreased hypertrophic adipocyte resulted in decreased adipokine secretion, which has been associated with the suppression of obesity-associated comorbidities and vascular cell inflammation. The bioefficacy and lipolytic potential of water-soluble punicalagin have been improved after functional modification into NLCs.
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Objective: To evaluate COVID19 patients' clinical characteristics, risk factors, and COVID-19 severity at baseline and over one month following hospitalization. Design setting and participants: This prospective cohort study of 598 Saudi COVID19 patients recruited from 4 major medical institutions nationwide between June 01, 2020, and February 28, 2021. Patients were stratified into different demographic characteristics and COVID-19 severity scale. Results: Of the 598 hospitalized adult COVID19 patients (mean [range] age, 57 [46 to 65] years; 59% male), 300 (50.16%) had severe clinical COVID-19. Comorbidity was high among hospitalized patients (73.5 %), with diabetes mellitus (n=; 46%) and hypertension (n=; 41%) being the most common prevalent. In a multivariate logistic regression model, patient demographics and clinical factors such as age (odds ratio [OR], 1.014 per year; 95% CI, 1.003-1.025), male sex (OR, 1.63; 95% CI, 1.02-2.62), diabetes mellitus (OR, 1.63; 95% CI, 1.06-2.49), obesity (OR, 1.93; 95% CI, 1.26-2.94), oxygen saturation<92% (OR, 4.83; 95% CI, 2.96-7.86), and high neutrophil to lymphocyte ratio (OR, 3.74 per unit; 95% CI, 1.96-7.14) were independently associated with higher COVID-19 severity. Moreover, more than 60% of male patients and middle-aged patients (40-60 years) were associated with the use of COVID-19 medications, including favipiravir and dexamethasone, during their hospital stay. Additionally, the rate of invasive mechanical ventilation was the highest in female patients (61.5%) and in middle-aged patients (46.2%). However, the death rate was slightly higher in males (56%) than in female patients and in elderly patients (52%). In Cox proportional analysis, age associated with increased risk of 60-days mortality (Hazard ratio; HR, 1.05 per year; 95% CI, 1.018-1.098). Additionally, the Riyadh region associated with more COVID-19 cases required invasive respiratory support (57.7%) and Jeddah was associated with more deceased COVID-19 cases (44%). Conclusions: The data shows that comorbidity is associated with hospitalization among COVID-19 patients, which indicates the level of severity. Infection during the winter season (November), male gender, elderly, and those with pre-existing diabetes mellitus or obesity were associated with higher COVID-19 clinical severity.
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Objectives: There are limited data on the efficacy and safety of favipiravir antiviral in coronavirus disease 2019 (COVID-19), particularly in the more progressed disease phase. This study aims to evaluate the favipiravir effect on reducing the length of hospital stay and in-hospital mortality among moderate and severe hospitalized COVID-19 patients. Methods: A prospective, multicenter observational study was conducted that included moderate and severe hospitalized adult COVID-19 patients in four major regions (Riyadh (Riyadh), Eastern (Dammam), Al-Qassem (Buraydah), and Macca (Jeddah) of Saudi Arabia. For the primary outcome of all-cause mortality, a Cox proportional hazard analysis was performed. While the association between favipiravir use and length of hospital stay was determined using adjusted generalized linear model. This study was approved by the Central Institutional Review Board in The Saudi Ministry of Health (MoH) with the approval number IRB # 20-85-M. Results: This study included 598 moderate and severe COVID-19 patients, of whom 156 (26%) received favipiravir. Favipiravir treatment was associated with more extended hospital stays (14 vs. 10 median days, P = 0.034) and higher mortality rate (aHR 3.63; 95% CI 1.06-12.45) compared to no favipiravir regimen. Despite lack of effectiveness, favipiravir use was only associated with higher diarrhea adverse effects (12 vs. 5%, P = 0.002), but it did not affect the renal and liver profiles of patients. Conclusion: Favipiravir was ineffective in reducing the length of hospital stay and in-hospital mortality in patients with moderate and severe COVID-19.
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Bernard-Soulier syndrome is a rare autosomal recessive bleeding disorder and has a low incidence. Bernard-Soulier syndrome is caused by the deficiency of glycoprotein GPIb-V-IX complex, a receptor for von Willebrand factor and is characterized by thrombocytopenia, giant platelets and bleeding tendency. We are reporting three members of a same family with variable phenotypic clinical presentation. The index case is a 20-year-old boy who has a frequent presentation with epistaxis, and low platelet counts (25â×â109/l). He had been hospitalized multiple times and received platelet transfusions. His brother and cousin reported bleeding symptoms with less frequent medical intervention. Genetic analysis by next-generation sequencing identified a homozygous GP1BB variant (c.423C>A:p.Cys141Ter), which segregated amongst the family members. The results led us to an improved insight into the disease for this family with variable phenotypic expression, in addition to the identification of a variant for further structural and functional characterization.
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Síndrome de Bernard-Soulier/genética , Mutação com Perda de Função , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Adulto , Feminino , Homozigoto , Humanos , Masculino , Linhagem , Adulto JovemRESUMO
Methylenetetrahydrofolate reductase (MTHFR) polymorphism plays a fundamental role in susceptibility to various diseases, including cancers and autoimmune diseases. In the current study, we aimed to compare genotype and allele frequency variations of rs1801131, one of the most common variants found in the MTHFR gene, among Saudi smokers and non-smokers. We hypothesized that genetic variations of this gene are responsible for many diseases, particularly those caused by cigarette smoking (CS) such as pulmonary diseases, oral cancer and lung cancer. We performed a case-control study on a sample of 235 healthy smokers and 239 healthy non-smokers in Saudi Arabia. The rs1801131 SNP genotypes were determined using a genotyping assay and multiple in silico algorithmic software programs were used to identify the effects and structural functions of the rs1801131 (Glu429Ala) mutation. Using chi-squared tests, we found that, among smokers, TG and GG genotype carriers had 0.209-fold (OR = 0.209, P < 0.005) and 0.427-fold (OR = 0.427, P = 0.003) lower risks of CS-related disease compared to TT reference genotypes. In addition, this protective effect was observed in Saudi smokers independent of age, gender, types of smoking, duration, and average daily smoking consumption. Filling a research gap by exploring this topic in the Saudi population, the current findings indicate that genotype and allele distributions of MTHFR rs1801131 polymorphism present fundamental protective effects against the risk of CS-related disease. These findings should be verified in future studies with larger sample sizes, different ethnicities, and patients suffering from CS-related diseases, such as oral cancer and lung cancer.
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Cigarette smoking is a major lifestyle factor leading to different human diseases. The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA. Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes. Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients. Four TDG SNPs-rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population. The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (>5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers. Also, in smokers aged less than 29 years, the "CT," "TT," and "CT + TT" alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6, 4, and 5 times, respectively, in contrast with the ancestral "CC" homozygous allele. A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities. Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population. In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene. This variation on TDG SNP's with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population.
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Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Fumar/genética , Timina DNA Glicosilase/genética , Adulto , Alelos , Etnicidade/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , MasculinoRESUMO
ABSTRACT: Prevalence of bleeding disorders vary due to several factors including geographical location. Mild bleeding disorders can lead to iron deficiency, morbidity, and in severe cases mortality. Quantification of haemorrhagic symptoms is a key component in management of bleeding disorders and a challenging task for clinicians.An abridged version of MCMDM-1vWD questionnaire with validated Arabic translation was used to quantify bleeding disorders in adult students (nâ=â1138) in 4 different regions of Kingdom of Saudi Arabia. Statistical analysis was performed to indicate gender disparity and prevalence.74.5% of respondents answered at least 1 question with affirmation, with 32.3% affected in Riyadh showing the highest prevalence and 14.03% affected in Dammam showing the least prevalence (P-valueâ<â.001). Gender-wise, higher prevalence of bleeding disorders in females 54.9% than in males 45.1% was observed (P-value .01). Epistaxis prevalence was significantly higher in males 30.7% vs 23.2% in females (P-value .0004), while cutaneous symptoms were reported significantly more by female participants 29.7% vs 12.3% in males (P-valueâ<â.001). Menorrhagia was reported by 28% of females, with heavy bleeding experienced by 57.6% female participants forâ<7âdays while in 42.4% of females for >7âdays.The current study signifies the ethnic distribution and gender disparity of mild bleeding disorders, and highlights the need for national surveillance system in order to improve management of patients with bleeding disorders.
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Hemorragia/epidemiologia , Adolescente , Adulto , Estudos Transversais , Epistaxe/epidemiologia , Feminino , Humanos , Masculino , Menorragia/epidemiologia , Prevalência , Arábia Saudita/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Estudantes de Medicina/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: The one-stage assay is the most common method to measure factor VIII activity (FVIII : C) in hemophilia A patients. The chromogenic assay is another two-stage test involving purified coagulation factors followed by factor Xa-specific chromogenic substrate. AIM: This study aimed to assess the discrepancy and correlation between the chromogenic and one-stage assays in measuring FVIII : C levels in hemophilia patients receiving Extended Half-Life Elocta® as a recombinant extended half-life coagulation factor. METHODS: We performed a study comparing the measurements of FVIII : C levels by the chromogenic versus the one-stage assays at different drug levels. Data of FVIII : C levels, dosage, and the time interval from administration to measurement were retrieved from the hospital records. The correlation, mean differences, and discrepancy between the two assays were calculated. The linear regression analysis was used to predict the time interval till reaching 1% FVIII : C. RESULTS: Fourteen patients with 56 samples were included in the study. Of them, 13 patients were receiving Elocta® as a prophylactic, while one was receiving Elocta® on demand. One-third of these samples showed a discrepancy between the chromogenic and one-stage assays. The two assays were well correlated. Mean differences were significant at the individual and the time interval level. The time since the last Elocta® injection could significantly predict FVIII : C levels (ß = 0.366, P < 0.001). CONCLUSION: Our findings suggested a significant difference between both methods; the FVIII : C levels measured by the one-stage assay were less than those estimated by the chromogenic assay. However, the measurements of FVIII levels by the two assays were well correlated but discrepant in one-third of the samples. The levels of FVIII : C reach 1% after 5.4 days since the last Elocta® administration.
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Introduction Inherited bleeding disorders vary in prevalence due to genetic disparity and ethnicity. Little is known about the prevalence of coagulation factor deficiency and bleeding disorders in middle-eastern population. Methods Young Saudi adults with at least one positive bleeding symptom reported in semi-structured validated condensed MCMDM-1vWD questionnaire were tested for complete blood count, routine and special coagulation tests, serum ferritin level, and capillary zone electrophoresis. After initial testing, those with prolonged prothrombin time (PT) or activated prothrombin time (APTT) had further testing to evaluate coagulation factors level. Platelet function was tested through platelet function analyzer (PFA)-100, and multiplate aggregometer (MEA) on patients suspected of having platelet disorders. Results Six-hundred-forty patients (male = 347, 54.2%) were included. A possible platelet function defect was diagnosed in three patients with one matching Glanzmann's thrombasthenia trait pattern, and one that of Bernard-Soulier trait pattern. One patient was diagnosed with von Willebrand disease. Deficiencies in coagulation factor levels were revealed as F-VIII in 14 (7.4%), F-IX in 15 (7.6%), F-II in two (3.3%), F-V in 17 (26.1%), FVII in two (3.1%), and F-X in one (1.8%) of study subjects; low vWF activity (<50%) was found in 14 (8%). Abnormal values were found for various laboratory tests with prolongation of platelet function analyzer-epinephrine (PFA-EPI) in 11%, PFA-ADP or arachidonic acid in 15.2%, PT in 35.9%, and APTT in 63.7%. Five-hundred-seventy-six patients (90%) had normal results in the coagulation factor assays and were categorized as patients with bleeding of unknown cause (BUC). A diagnosis of a bleeding disorder was more frequently made in men than in women (38 vs. 26). Iron deficiency anemia was found in 18 (25%) females positively associated with F-IX deficiency ( p -value 0.000). Male gender (73.3%, p = 0.007) was independently associated with the diagnosis of coagulation factor deficiency. Conclusion The current study reports a higher prevalence of coagulation factors deficiency in Saudi population than reported in the western population.
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Mutant alleles of CDH23, a gene that encodes a putative calcium-dependent cell-adhesion glycoprotein with multiple cadherin-like domains, are responsible for both recessive DFNB12 nonsyndromic hearing loss (NSHL) and Usher syndrome 1D (USH1D). The encoded protein cadherin 23 (CDH23) plays a vital role in maintaining normal cochlear and retinal function. The present study's objective was to elucidate the role of DFNB12 allelic variants of CDH23 in Saudi Arabian patients. Four affected offspring of a consanguineous family with autosomal recessive moderate to profound NSHL without any vestibular or retinal dysfunction were investigated for molecular exploration of genes implicated in hearing impairment. Parallel to this study, we illustrate some possible pitfalls that resulted from unexpected allelic heterogeneity during homozygosity mapping due to identifying a shared homozygous region unrelated to the disease locus. Compound heterozygous missense variants (p.(Asp918Asn); p.(Val1670Asp)) in CDH23 were identified in affected patients by exome sequencing. Both the identified missense variants resulted in a substitution of the conserved residues and evaluation by multiple in silico tools predicted their pathogenicity and variable disruption of CDH23 domains. Three-dimensional structure analysis of human CDH23 confirmed that the residue Asp918 is located at a highly conserved DXD peptide motif and is directly involved in "Ca2+" ion contact. In conclusion, our study identifies pathogenic CDH23 variants responsible for isolated moderate to profound NSHL in Saudi patients and further highlights the associated phenotypic variability with a genotypic hierarchy of CDH23 mutations. The current investigation also supports the application of molecular testing in the clinical diagnosis and genetic counseling of hearing loss.
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Caderinas/genética , Surdez/genética , Adolescente , Adulto , Alelos , Proteínas Relacionadas a Caderinas , Caderinas/metabolismo , Surdez/fisiopatologia , Família , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Mutação/genética , Mutação de Sentido Incorreto/genética , Linhagem , Retinose Pigmentar/genética , Arábia Saudita , Síndromes de Usher/genética , Sequenciamento do Exoma/métodosRESUMO
Iron deficiency is the most prevalent nutritional deficiency worldwide. According to an estimate by the World Health Organization, up to 27% of the world's population experience iron deficiency anemia (IDA). Studies conducted in the Middle East, including Saudi Arabia, have suggested that IDA is the most common cause of anemia, especially among females. This study aimed to determine the prevalence of IDA and iron deficiency (ID) among apparently healthy young university students from four regions in Saudi Arabia. Students were asked to complete a simple survey questionnaire; blood samples were then collected and analyzed after obtaining informed consent. A total of 981 students completed the survey, with 11% of the participants reporting symptoms of anemia; 34% of participants were diagnosed with IDA and 6% reported a diagnosis of hemoglobinopathy. Blood analysis confirmed the prevalence of ID and IDA in 28.6% and 10.7% of the participants, respectively; those with ID and IDA were mostly females (88.5% and 94%, resp.). Thalassemia trait and sickle cell trait were detected in 1.3% and 7% of participants, respectively. Our findings from a national survey among young university in Saudi Arabia indicate a high prevalence of ID and IDA.
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BACKGROUND: BRCA1/2 pathogenic variants have become associated with familial breast and ovarian cancers, and hereditary cancer-predisposition syndrome. With advances in molecular biology, BRCA profiling facilitates early diagnosis and the implementation of preventive and therapeutic strategies. The genes exhibit variable prevalence among different individuals and moderate interpretation complexity. BRCA deficiency is instrumental in cancer development, affects therapeutic options and is instrumental in drug resistance. In addition, BRCA1/2 profile is diverse across different groups and has been associated with the "founder effect" in certain populations. METHODS: In this review, we aim to detail the spectrum of BRCA1/2 variants and their associated risk estimates. RESULTS: The relationship between BRCA1/2 and hereditary and familial cancers is indisputable, yet BRCA screening methods are beset with limitations and lack clinical confidence. CONCLUSION: This review emphasizes the importance of screening BRCA genetics, in addition to their clinical utility. Furthermore, founder variants are anticipated in the Saudi population.