Thalassemia — From Genotype to Phenotype

Thalassemia encompasses serious diseases with complex pathophysiology that is difficult to explain since it is considered a group of defects with similar clinical effects, still not a single disorder

Craniofacial anthropometric measurements of the cohort of Egyptian male school children and their utility in detection of abnormalities

ABSTRACT: Background Anthropology is a scientific discipline which applies scientific methods to identify and quantitate inter-individual variations in body structure and function. Anthropometry assesses craniofacial dysmorphology in genetic disorders and helps to detect phenotypic differences in diseases with common underlying cause. This study is part of a comprehensive cross-sectional study of craniofacial and oral findings in Egyptian school children. This paper focused on establishing the norms of Egyptian male school children and its utility in determining the differences in facial measurements of a child with Prader–Willi syndrome (PWS). Thirty craniofacial measurements were taken from 55 healthy Egyptian school children aged 12–14 years with mean age 13 ± 0.64 and a PWS child aged 13.6 years. The PWS measurements were compared with healthy children of the same age using computed Z-score. Results Morphological face height of the PWS child was within the normal range. However, upper face height and nose height were significantly lower with Z-scores of - 3.18 and - 2.7, respectively; right and left mandibular body length and upper lip height were significantly higher than the mean of healthy children with corresponding Z-scores of 2.95, 2.48, and 2.33. Conclusions By establishing the norms of Egyptian male school children and utilizing these data, we can identify the difference in facial measurements among children with abnormalities like PWS. This information can be used during periodic checkups as a simple, non-invasive, and economical method for the detection of these abnormalities

Developing a Road Map to Spread Genomic Knowledge in Africa: 10th Conference of the African Society of Human Genetics, Cairo, Egypt

The tenth conference of the African Society of Human Genetics was held in Egypt with the theme “Human Genetics and Genomics in Africa: Challenges for Both Rare and Common Genetic Disorders.” Current research was presented, and we discussed visions for the future of genomic research on the African continent. In this report, we summarize the presented scientific research within and relevant to Africa as presented by both African and non-African scientists. We also discuss the current situation concerning genomic medicine and genomic research within the continent, difficulties in implementing genetic services and genomic medicine in Africa, and a road map to overcome those difficulties and meet the needs of the African researchers and patients

Genomic alterations in the F8 gene correlating with severe hemophilia A in Egyptian patients

Abstract Background Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients. Methods DNA samples from 60 HA patients were screened for int22 and int1 rearrangements using simplified inverse shifting PCR (IS‐PCR) followed by exon 14 sequencing. Also, four uncharacterized patients were studied by targeted exome sequencing. Results In 33.3% of the studied patients, we identified three int22 rearrangements, three exon 14 mutations (two frameshift; one novel (NM_000132.3:c.2734_2735delAA, p.(N912Ffs*6)), a second reported mutation (NM_000132.3:c.3091_3094delAGAA, p.(K1031Lfs*9)), and one nonsense mutation (NM_000132.3:c.2440C>T, p.(R814*)). All identified mutations were detected in patients with severe HA phenotype. Targeted exome sequencing could not detect any known pathogenic variants. Conclusion Intron 22 rearrangement and exon 14 mutations correlate with most severe hemophilia A Egyptian patients

Genetic and Molecular Evaluation: Reporting Three Novel Mutations and Creating Awareness of Pycnodysostosis Disease

Pycnodysostosis is a rare autosomal recessive disorder with characteristic diagnostic manifestations. This study aims to phenotype and provide molecular characterization of Egyptian patients, with emphasis on identifying unusual phenotypes and raising awareness about pycnodysostosis with different presentations to avoid a mis- or under-diagnosis and consequent mismanagement. We report on 22 Egyptian pycnodysostosis patients, including 9 new participants, all descending from consanguineous families and their ages ranging from 6 to 15 years. In addition, prenatal diagnosis was performed in one family with affected siblings. They all presented with short stature, except for one patient who presented with pancytopenia as her primary complaint. Moreover, 41.2% of patients had sleep apnea, 14% presented with craniosynostosis, and 44.4% had failure of tooth development. Molecular analysis via direct exome sequencing of the cathepsin K gene revealed three novel mutations ((NM_000396.3) c.761_763delCCT, c.864_865delAA, and c.509G>T) as well as two previously reported mutations among nine new cases. The following is our conclusion: This study expands the molecular spectrum of pycnodysostosis by identifying three novel mutations and adds to the clinical and orodental aspects of the disease. The link between the CTSK gene mutations and the failure of tooth development has not been established, and further studies could help to improve our understanding of the molecular pathology

Gene mutations of the three ectodysplasin pathway key players (EDA, EDAR, and EDARADD) account for more than 60% of Egyptian ectodermal dysplasia: A report of seven novel mutations

Ectodermal dysplasia (ED) is a diverse group of genetic disorders caused by congenital defects of two or more ectodermal-derived body structures, namely, hair, teeth, nails, and some glands, e.g., sweat glands. Molecular pathogenesis of ED involves mutations of genes encoding key proteins of major developmental pathways, including ectodysplasin (EDA) and wingless-type (WNT) pathways. The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. Molecular diagnosis is fundamental for disease management and emerging treatments. We used targeted next generation sequencing to study EDA, EDAR, EDARADD, and WNT10A genes in 45 Egyptian ED patients with or without hypohidrosis. We present genotype and phenotype data of 28 molecularly-characterized patients demonstrating genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability. Thirteen mutations were reported, including four novel EDA mutations, two novel EDARADD, and one novel EDAR mutations. Identified mutations congregated in exons encoding key functional domains. EDA is the most common gene contributing to 85% of the identified Egyptian ED genetic spectrum, followed by EDARADD (10%) and EDAR (5%). Our cohort represents the first and largest cohort from North Africa where more than 60% of ED patients were identified emphasizing the need for exome sequencing to explore unidentified cases