Search

PURPOSEThe terminology used for gene-disease curation and variant annotation to describe inheritance, allelic requirement, and both sequence and functional consequences of a variant is currently not standardized. There is considerable discrepancy in the literature and across clinical variant reporting in the derivation and application of terms. Here we standardize the terminology for the characterization of disease-gene relationships to facilitate harmonized global curation, and to support variant classification within the ACMG/AMP framework.METHODSTerminology for inheritance, allelic requirement, and both structural and functional consequences of a variant used by Gene Curation Coalition (GenCC) members and partner organizations was collated and reviewed. Harmonized terminology with definitions and use examples was created, reviewed, and validated.RESULTSWe present a standardized terminology to describe gene-disease relationships, and to support variant annotation. We demonstrate application of the terminology for classification of variation in the ACMG SF 2.0 genes recommended for reporting of secondary findings. Consensus terms were agreed and formalized in both sequence ontology (SO) and human phenotype ontology (HPO) ontologies. GenCC member groups intend to use or map to these terms in their respective resources.CONCLUSIONThe terminology standardization presented here will improve harmonization, facilitate the pooling of curation datasets across international curation efforts and, in turn, improve consistency in variant classification and genetic test interpretation.

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52–59% (31–35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.

Hereditary spinocerebellar degenerative disorders (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include spastic paraplegia, spastic ataxia, cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 patients from 38 unrelated Sudanese families segregating multiple forms of SCDs focusing on known human disease-associated genes. We reached the genetic diagnosis in 63% and up to 73% of the studied families when considering variants of unknown significance. Taking into account a series of Sudanese families that we previously analyzed, the combined success rate in the two series reached 52–59% (31–35/59 families). We also highlighted the genetic and clinical heterogeneity of SCDs in Sudan, as we identified no single major gene in our cohort and the potential for discovering novel SCDs genes in this population.

Penelitian ini menggunakan pendekatan kualitatif, dengan rancangan studi kasus fenomenologis. Analisis data yang digunakan yaitu analisis fenomenologis. Hasil penelitian terhadap respon guru SDN 10 Pajo tentang pelanggaran siswa yaitu: 1) Pelanggaran siswa adalah perilaku menyimpang yakni dengan melanggar peraturan sekolah, sehingga mengganggu suasana belajar dan merugikan individu lain; 2) Bentuk pelanggaran siswa dikategorikan menjadi 2, yaitu perilaku mengganggu dan pelanggaran serius siswa. 3) terdapat 6 penyebab pelanggaran siswa yaitu: kondisi fisik, kurangnya perhatian orang tua (pendidikan moral dan dukungan ekonomi), metode pembelajaran guru yang kurang bervariasi (monoton), bahasa yang sulit dipahami siswa, lingkungan negatif, dan materi pelajaran terlalu banyak; 4) Cara mengatasi pelanggaran siswa, yaitu: pemberian model bagi siswa, teguran verbal, sanksi fisik, perhatian khusus, memanipulasi pemberian tugas, memberikan aktivitas pengganti, memanipulasi lokasi tempat duduk, memberikan pemahaman khusus, memberikan kisi-kisi belajar, berkomunikasi dengan orang tua, memberikan peraturan, memberikan pilihan baik-buruk, pembiasan, memberikan pengalaman gagal, memberikan motivasi, berkomukasi secara pribadi dengan siswa, dan dikembalikan kepada orang tua.

The corticotropin-releasing hormone receptor 2 (

Background Major Depressive Disorder (MDD) and Type 2 Diabetes (T2D) are heterogeneous polygenic and complex disorders and are often comorbid. This shared comorbidity can be partially explained by several genetic, environmental, and hormonal factors such as hypercortisolism in MDD and a subset of patients with T2D. CRH receptor-1 (CRHR1) dysfunction may explain the MDD- and T2D-hypercortisolism, at least in a subgroup of patients. CRHR1-variants predisposing to impaired CRHR1 dosage and/or function may lead to hypercortisolism (substrate for serotonin dysfunction and MDD), as well as hyperglycemia, insulin resistance, and increased visceral fat, all T2D-traits. We hypothesize that CRHR1-variants may impair the stress and cortisol response, conferringincreased risk for MDD, T2D, and MDD-T2D comorbidity. Methods Using 212 Italian families with T2D, enriched T2D-familial history, and MDD, we amplified and tested 158 CRHR1 SNPs by two-point parametric analysis for linkage and linkage-disequilibrium (LD), using the models dominant (D) and recessive (R), with complete (1) and incomplete (2) penetrance (Pseudomarker). Results We detected linkage to and/or LD with MDD: for 93 SNPs (D1), 57 SNPs (D2), 91 SNPs (R1), and 14 (R2); and T2D for 15 SNPs (D1), 18 SNPs (D2), twelve SNPs (R1) and ten SNPs (R2), for a total of 122 SNPs. Specific LD-blocks’ underlined each disorder without overlap. Of note, three independent SNPs were comorbid forMDD and T2D. All risk SNPs are intronic, except for one synonymous, one splice site, one missense, and one 3'UTR. In-silicoanalysis detected functional gene and tridimensional protein changes in a risk-SNP. Conclusion We are the first to report CRHR1 in linkage and LD with MDD and T2D in T2D-families. CRHR1contribution to MDD appears stronger thanthe contribution to T2D and may thus antecede its onset . Genetically impaired stress and cortisol response may lead to comorbid MDD-T2D, likely a molecular-clinical entity in a subset of families. Our findings should be replicated in families from other ethnic groups. Presentation: No date and time listed

Introduction: University of Khartoum (U of K) is the largest and oldest university in Sudan (1). The recent rankings of international and local universities made by Webometrics Ranking of world Universities initiative in 2017 have placed University of Khartoum as number one University in Sudan and 1970 in rank Worldwide. This ranking system is based mainly on research activity and publications. Using PubMed we obtained data on all PubMed-indexed articles (from 1966 to 2016) affiliated to the four oldest and most established Sudanese universities: University of Khartoum, University of Gezira, Omdurman Islamic University, and Al-Neelain University. Methods: Using R Statistical environment, we compiled a unified dataset from multiple resources including PubMed data and impact factor data. This unified dataset was then used to calculate multiple article and authorship metrics including total number of articles and annual averages. We also applied text mining techniques to from indexed abstracts in order to explore the prevailing trends and research focus of some the most prolific authors and to visualize this trends though word clouds. Results: Since the earliest date of PubMed indexing in 1966, the University of Khartoum is by far the most affiliated Sudanese university in PubMed. Approaching 300 articles in 2016, the number of PubMed indexed articles has shown a promising rising trend over the past decade. Our results clearly indicate lead of University of Khartoum in published biomedical research. This trend is promising and shows the attention shift towards research activities among the major Sudanese universities in general and University of Khartoum in particular.

PURPOSESeveral groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease, and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed.METHODSThe GenCC drafted harmonized definitions for differing levels of gene-disease validity based on existing resources, and performed a modified Delphi survey with three rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members.RESULTSBased on 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contains 15,241 gene-disease assertions on 4,569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%.CONCLUSIONTerminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.

Congenital muscular dystrophies (CMD) are a heterogeneous group of disorders caused by mutations in musculoskeletal proteins. The most common type of CMD in Europe is Merosin-deficient CMD caused by mutations in laminin-α2 protein. Very few studies reported pathogenic variants underlying these disorders especially from Africa. In this study we report a rare variant (p.Arg148Trp, rs752485547) in LAMA2 gene causing a mild form of Merosin-deficient CMD in a Sudanese family. The family consisted of two patients diagnosed clinically with congenital muscular dystrophy since childhood and five healthy siblings born to consanguineous parents. Whole exome sequencing was performed for the two patients and a healthy sibling. A rare missense variant (p.Arg148Trp, rs752485547) in LAMA2 gene was discovered and verified using Sanger sequencing. The segregation pattern was consistent with autosomal recessive inheritance. The pathogenicity of this variant was predicted using bioinformatics tools. More studies are needed to explore the whole spectrum of mutations in CMD in patients from Sudan and other parts of the world.

Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1 variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T G, p.Ile324Ser; c.344 T C, p.Phe115Ser; and c.881 C T, p.Pro294Leu), one duplication (c.831_838dupATATCTGT, p.Ser280Tyrfs*8), and one synonymous/splicing-site mutation (c.762 C T, p.Ser254). The segregation pattern was consistent with autosomal recessive inheritance. The clinical presentation and brain MRI of the seven affected patients were consistent with the diagnosis of MLC1. Due to the high frequency of distinct MLC1 mutations found in our leukodystrophic Sudanese families, we analyzed the coding sequence of MLC1 gene in 124 individuals from the Sudanese genome project in comparison with the 1000-genome project. We found that Sudan has the highest proportion of deleterious variants in MLC1 gene compared with other populations from the 1000-genome project.

Background Mitochondrial maternally inherited hearing impairment (HI) appears to be increasing in frequency. The incidence of mitochondrial defects causing HI is estimated to be between 6 and 33% of all hearing deficiencies. Mitochondrial m.1555A > G mutation is the first mtDNA mutation associated with non-syndromic sensorineural deafness and also with aminoglycoside induced HI. Its prevalence varied geographically between different populations. Methods We carried out PCR, restriction enzyme based screening, and sequencing of 337 subjects (including 132 patients diagnosed clinically with hereditary deafness) from 54 families from Syria for m.1555A > G mitochondrial mutation. Results Mitochondrial m.1555A > G mutation was detected in one of fifty-four families (1.85%), six out of the 132 (4.5%) of all patients with NSHI and one propositus of the 205 individuals with normal hearing (0.48%). Conclusion This is the first study to report prelingual deafness causative gene mutations identified by sequencing technology in Syrian families. It is obvious from the results that the testing for the m.1555A > G mutation is useful for diagnosis of hearing loss in Syrian patients and should also be considered prior to treatment with aminoglycosides in predisposed individuals.

BackgroundBurkitt’s lymphoma (BL) is an aggressive form of B-cell non-Hodgkin lymphoma. Endemic subtype of the disease showed a remarkable statistical and epidemiological association with malaria infection. Despite the numerous studies performed to explain this association; molecular mechanisms underlie such coincidence still remain unclear. Dissecting molecular mechanisms which link Malaria infection and Burkitt’s lymphoma can provide insights about reported anticancer action of certain antimalarial drugs, namely artemisinin derivatives.MethodsHere we applied an integrative approach to investigate for potential links between malaria infection and endemic Burkitt’s lymphoma regarding their gene expression, and further explore common molecular mechanisms through which artemisinin compounds might act in endemic Burkitt’s lymphoma. Using gene expression data of malaria (Plasmodium falciparum infected erythroblasts) and endemic Burkitt’s lymphoma from Gene Expression Omnibus database, expression patterns in the two conditions were examined through clustering analysis using Self Organizing Maps, and then by significance testing of differentially expressed genes in each condition followed by Functional annotation using Gene Ontology clustering and Pathways analysis.ResultsClustering analysis identified a significant overlap between the expression patterns in endemic Burkitt’s lymphoma and Plasmodium falciparum infected cells. Four out of the 12 identified clusters contained genes with similar expression patterns in both conditions. Differential expression analysis identified 1689 genes as significantly differentially expressed in endemic Burkitt’s lymphoma and 405 in malaria. Those genes were found to be related to important Gene Ontology terms and pathways. Interestingly 65% of the identified pathways in Malaria were overlapped with those identified in endemic Burkitt’s lymphoma. Several of these pathways reported to be related to actions of artemisinin derivatives.ConclusionOur In-silico analysis showed a significant molecular convergence between endemic Burkitt’s lymphoma and malaria. A number of 43pathways which demonstrated enrichment in tumour were shared with Plasmodium falciparum infected erythrocytes. Such pathways represent potential targets for antimalarial drugs to exert therapeutic effects in such malignancy.

Background The conventional variant calling of pathogenic alleles in exome and genome sequencing requires the presence of the non-pathogenic alleles as genome references. This hinders the correct identification of variants with minor and/or pathogenic reference alleles warranting additional approaches for variant calling. Results More than 26,000 Exome Aggregation Consortium (ExAC) variants have a minor reference allele including variants with known ClinVar disease alleles. For instance, in a number of variants related to clotting disorders, the phenotype-associated allele is a human genome reference allele (rs6025, rs6003, rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current variant calling standards miss homozygous reference disease variants in these sites and provided a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We present exome sequencing results from an individual with venous thrombosis to emphasize how pathogenic alleles in clinically relevant variants escape variant calling while non-pathogenic alleles are detected. Conclusions This article highlights the importance of specialized variant calling strategies in clinical variants with minor reference alleles especially in the context of personal genomes and exomes. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state. Electronic supplementary material The online version of this article (10.1186/s12864-018-4433-3) contains supplementary material, which is available to authorized users.

International audience; Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent.Case presentation: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members.Conclusion: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients’ phenotype). Therefore this variant can be currently annotated as “pathogenic”. This is the first study to report mutations in PLA2G6 gene in patients from Sudan.

Background: Asthma is a complex disorder with heterogeneous phenotypes attributed to the interactions of many genes and the environment. Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-q33. This study aimed to determine the association of 10 candidate polymorphisms in IL-4, IL-5, IL-9, IL-13 and IL-4R genes in 5q31-q33 region with susceptibility to asthma in Sudanese families.Method: Fifty two multi cases families consisting of 141 known cases of asthma and 129 healthy individuals from Khartoum state were genotyped for seven SNPs on 5q31-33 region located in four candidate genes; IL4, IL5 IL13, IL9 and three SNPs in IL4Rα on chromosome 16p using multiplex PCR with Mass ARRAY system. Multiple logistic regression was used to test for association of asthma. P-value needed to achieve statistical significance taking multiple testing into account is P=0.005 (=0.05/10 (number of SNPs genotyped)). However, since SNPs within genes showed some degree of linkage disequilibrium and SNPs were selected as major SNPs for association with Asthma in other populations. Therefore, P £ 0.01 (=0.05/5 genes) can used as the P-value required to achieve correction for multiple testing.Result: Genotype and allelic frequencies of all SNPs were similar in both asthmatics and healthy subjects. Stepwise logistic regression demonstrated that SNP IL-13 rs2069743 was markedly associated with Asthma (P=0.008) and same SNP added significant main effects to IL-4 rs2070874 or IL-9 rs31563, whereas the reverse was not true, indicating that the main effect for association with asthma in this population is most strongly tagged by SNP IL-13 rs2069743.Conclusion: There is strong genetic association of SNPs in 5q31-q33 and 16p11 region and asthma.

International audience; Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central nervous system characterized by lower limb spasticity, cerebellar ataxia and involvement of the dorsal column. The disease is caused by mutations in the DARS2 gene but has never been reported in sub-Saharan Africa so far.Case presentation: Two siblings, aged 18 years and 15 years, from a consanguineous family presented with pyramidal signs and symptoms since infancy and developmental delay. Whole exome sequencing of the proband identified two compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2. Sanger sequencing confirmed the presence of the mutations and their segregation in trans in both patients and in their elder sister (aged 20 years), who showed only brisk reflexes and mild lower limb spasticity. Surprisingly, in contrast to her subtle clinical presentation, the elder sister had abnormal MRI features and serum lactate levels comparable to her ill sisters.Conclusion: This report illustrates intra-familial phenotypic variation in LBSL and provides an example of a marked dissociation between the clinical and radiological phenotypes of the disease. This may have implications for the detection of mutation carriers in LBSL.

Vitamin C is a water-soluble compound with anti-oxidant properties that is essential for collagen synthesis and protection of living organisms against oxidative stress. These important roles, and the relatively large amounts of vitamin C required daily, likely explain why most vertebrate species are able to synthesize it but surprisingly; many species of anthropoid primates, guinea pigs, as well as some bats have lost the capacity to synthesize it. We hypothesized that the loss of vitamin C synthesis in early primate ancestors contributed to their relatively long life spans through up-regulation of hypoxia induced factor 1α (HIF1α), a transcription factor that plays an essential role in cellular response to oxidative stress.

A group of SNPs in 5q31, genotyped from Hausa tribe of Koka village in eastern Sudan; an area endemic with malaria and visceral leishmaniasis, were analyzed by The Leishmaniasis research group and found to have significant excess of heterozygosis level and departure from HWE and assumed to be due to natural selection resulting from notorious deadly outbreaks since various ethnic groups from western Sudan settled the area although sequence information in the 5q31 region did not detect functional SNPs that could be associated with such drastic phenotypes. Malaria was thought to inflict inferior selective pressure due to the mild clinical phenotype observed. Taking advantage of follow up phenotype data sets available from the Malaria Gen study we re-analyzed these genotypes using different bioinformatics software to determine their effect on the regulation, function and expression of interleukins, miRNA binding and splicing mechanism. The SNPs were found to potentially affect the binding of many transcription factors that regulate the expression of IL-4 and IL-13 and stability of IL-5 mRNA. Association of haplotypes susceptibility revealed that the haplotype of low cytokine TH2 profile is associated with higher risk of malaria infection (P-value = 0.02). Through modulating TH2 cytokine response; the excess heterozygosity in 5q31 is explained with the phenomenon of overdominance between malaria and visceral leishmaniasis, acted by natural selection and driving the locus towards optimum response.

BACKGROUND Due to the recently observed rise in Plasmodium vivax incidence in Sudan and reported transmission in Duffy-negative individuals; we aimed to assess the possibility of P. vivax transmission in Duffy-negative individuals in Gezira state, central Sudan. METHOD A total of 126 suspected malaria patients were diagnosed with P. vivax infection using microscopy, RDT and PCR. PCR-RFLP was used to genotype participants Duffy status. RESULTS Forty eight (38%) were positive for P. vivax infection by PCR. Four patients (8.3%) were homozygous Duffy-negative. CONCLUSION These results confirm that P. vivax can infect Duffy-negative individuals, suggesting alternative mechanisms to bind and invade erythrocytes.

Recent understanding of the genetic basis of neurological disorders in Africa has grown rapidly in the last two decades. Africa harbors the largest genetic repertoire in the world which gives unique opportunity to discover novel variant, genes, and molecular pathways associated with various neurological diseases. Despite that, large-scale genomic and exome studies are severely lacking especially for neglected diseases such as leukodystrophies. This review aims to shed light on the currently developed research in leukodystrophies in Africa. We reviewed all research articles related to “Leukodystrophy in Africa” published in Medline/PubMed and Google Scholar databases up to date. We found very few studies in leukodystrophy from Africa, especially from the Sub-Saharan regions. Metachromatic leukodystrophy was the most studied type of leukodystrophy. Published studies from North Africa (Tunisia, Morocco, and Egypt) were very limited in either sample size (case studies or single/few family studies) or molecular methods (targeted sequencing or polymerase chain reaction-restriction fragment length polymorphisms). More studies (GWAS or large family studies) with advanced techniques such as exome or whole genome sequencing are needed to unveil the genetic basis of leukodystrophy in Africa. Unmasking novel genes and molecular pathways of leukodystrophies invariably lead to better detection and treatment for both Africans and worldwide populations.

Background Hearing impairments (HI) are the most common birth defect worldwide. Very large numbers of genes have been identified but the most profound is GJB2. The clinical interest regarding this gene is very pronounced due to its high carrier frequency (0.5–5.4%) across different ethnic groups. This study aimed to determine the prevalence of common GJB2 mutations in Syrian patients with profound sensorineural HI. Methods We carried out PCR, restriction enzyme based screening, and sequencing of 132 Syrian patients diagnosed clinically with hereditary deafness for different GJB2 mutations. Results The result revealed that, in GJB2 gene, c.35delG is the most prevalent among affected studied subjects (13.64%), followed by c.457G>A (2.4%). Conclusion The benefit of this study on the one hand is its first report of prelingual deafness causative gene mutations identified by sequencing technology in the Syrian families. It is obvious from the results that the deployment in biomedical research is highly effective and has a great impact on the ability to uncover the cause of genetic variation in different genetic diseases.

Background. Hearing impairments (HI) are the most common birth defect worldwide. Very large numbers of genes have been identified but the most profound is GJB2. The clinical interest regarding this gene is very pronounced due to its high carrier frequency (0.5–5.4%) across different ethnic groups. This study aimed to determine the prevalence of common GJB2 mutations in Syrian patients with profound sensorineural HI. Methods. We carried out PCR, restriction enzyme based screening, and sequencing of 132 Syrian patients diagnosed clinically with hereditary deafness for different GJB2 mutations. Results. The result revealed that, in GJB2 gene, c.35delG is the most prevalent among affected studied subjects (13.64%), followed by c.457G>A (2.4%). Conclusion. The benefit of this study on the one hand is its first report of prelingual deafness causative gene mutations identified by sequencing technology in the Syrian families. It is obvious from the results that the deployment in biomedical research is highly effective and has a great impact on the ability to uncover the cause of genetic variation in different genetic diseases.

In variation sites with minor reference alleles, overlooking the detection of homozygous reference genotypes results in inadequate identification of potential disease variants. Current variant calling practices miss these clinically relevant alleles warranting new approaches. More than 26,000 Eome Aggregation Consortium (ExAC) variants have a minor reference allele including 44 variants with known ClinVar disease alleles. We demonstrated how the current variant calling standards miss homozygous reference disease variants in these sites. We developed a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state.

Introduction. Parkinson's disease (PD) is a common neurodegenerative disorder. Mutations in PINK1 are the second most common agents causing autosomal recessive, early onset PD. We aimed to identify the pathogenic SNPs in PARK2 and PINK1 using in silico prediction software and their effect on the structure, function, and regulation of the proteins. Materials and Methods. We carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function. Result. Twenty-one SNPs in PARK2 gene were found to affect transcription factor binding activity. 185 SNPs were found to affect splicing. Ten SNPs were found to affect the miRNA binding site. Two SNPs rs55961220 and rs56092260 affected the structure, function, and stability of Parkin protein. In PINK1 gene only one SNP (rs7349186) was found to affect the structure, function, and stability of the PINK1 protein. Ten SNPs were found to affect the microRNA binding site. Conclusion. Better understanding of Parkinson's disease caused by mutations in PARK2 and PINK1 genes was achieved using in silico prediction. Further studies should be conducted with a special consideration of the ethnic diversity of the different populations.

Plasmodium falciparumis a predominant malaria species that infects humans in the African continent. A recent WHO report estimated 95% and 5% ofP. falciparumandP. vivaxmalaria cases, respectively, in Sudan. However many laboratory reports from different areas in Sudan indicated otherwise. In order to verify, we selected four hundred suspected malaria cases from Aljabalain area located in the White Nile state, central Sudan, and diagnosed them with quality insured microscopy and species-specific nested PCR. Our results indicated that the proportion ofP. vivaxinfections among suspected malaria cases was high. We found that on average 20% and 36.5% of malaria infections in both study areas were caused byP. vivaxusing both microscopy and PCR, respectively. This change in pattern is likely due to the recent demographic changes and high rate of immigration from neighbouring countries in the recent years. This is the first extensive clinical study of its kind that shows rising trend inP. vivaxmalaria cases in White Nile area, Sudan.

Introduction. Parkinson’s disease (PD) is a common neurodegenerative disorder. Mutations in PINK1 are the second most common agents causing autosomal recessive, early onset PD. We aimed to identify the pathogenic SNPs in PARK2 and PINK1 using in silico prediction software and their effect on the structure, function, and regulation of the proteins. Materials and Methods. We carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function. Result. Twenty-one SNPs in PARK2 gene were found to affect transcription factor binding activity. 185 SNPs were found to affect splicing. Ten SNPs were found to affect the miRNA binding site. Two SNPs rs55961220 and rs56092260 affected the structure, function, and stability of Parkin protein. In PINK1 gene only one SNP (rs7349186) was found to affect the structure, function, and stability of the PINK1 protein. Ten SNPs were found to affect the microRNA binding site. Conclusion. Better understanding of Parkinson’s disease caused by mutations in PARK2 and PINK1 genes was achieved using in silico prediction. Further studies should be conducted with a special consideration of the ethnic diversity of the different populations.