Medical Genetics

Orodental abnormalities in limb malformation syndromes: A review article Nehal F Hassib, Eman A AbulEzz, Magda Ramzy, Tarek El-Badry, Mona S Aglan, Samia A Temtamy Middle East Journal of Medical Genetics 2020 9(1):1-9 The regular synchronization during development of an embryo results in the normal formation of his/her structures. The deviation from this harmony produces malformations. The pleiotropic effects of similar genes that contribute in the growth of limb and oral structures produce concurrent abnormalities indeed. The present review gives a brief hint at the shared causative genes of both limb and orodental structures. The nosology either of skeletal and limb malformations or of orodental findings and the types of orodental anomalies were reported in these syndromes. Pathognomonic orodental features and Egyptian experiences are emphasized.

Quantification of hemoglobin peptides in Beta-thalassemia patients using tandem mass spectrometry for future national screening program Zeinab Y Abdallah, Soha S Nosier, Mona Ibrahim, Khalda Amr, Yasser Nassar, Ghada EL-Kamah Middle East Journal of Medical Genetics 2020 9(1):10-17 Background β-thalassemia is a hereditary blood disorder characterized by reduced or absent synthesis of the β chains of hemoglobin resulting in variable disease severity. The high carrier rate of thalassemia in Egypt makes it a priority genetic disease for prevention programs through detection of new cases and screening for carriers. Patients and methods In this study, for the first time in Egypt, tandem mass spectrometry (MS/MS) is used to distinguish patients with β-thalassemia from carriers and controls by calculation of α/β globin peptides ratio, as a contributory step in the management of this disease. The study included 40 patients with β-thalassemia referred from the Hereditary Blood Disorders Clinic, National Research Centre, 32 β-thalassemia carriers (parents of cases), and 34 healthy normal participants of matching age and sex. Dried blood spots from all participants were analyzed using MS/MS, followed by confirmatory molecular analysis. Results The results of MS revealed that α T1/β T1 globin peptides ratio is the most informative ratio that could be used to differentiate between β-thalassemia cases, carriers, and normal participants. The mean value of α T1/β T1 ratio for the studied cases was 4.24±0.97 (4.41±1.092 for thalassemia major and 3.83±0.88 for thalassemia intermedia), 1.93±0.30 for carriers, and 1.20±0.06 for controls, with statistical significant difference (P<0.001). Conclusion In conclusion, distinguishing patients from carriers and controls through tandem mass technology can serve as a cost-effective tool for national screening program for thalassemia in Egypt.

Effect of interleukin-10 polymorphism on susceptibility to type I diabetes in children with latent toxoplasmosis Raida S Yahya, Soha I Awad, Eman Hamed, Nanis S Elbeltagy, Rania A Abd Elazim Middle East Journal of Medical Genetics 2020 9(1):18-23 Objective The aim of this work was to investigate the effect of interleukin (IL)-10-1082 polymorphisms on susceptibility to type I diabetes in children with latent toxoplasmosis. Materials and methods IL-10 (−1082) polymorphisms were assessed by PCR in a small sample size of 75 patients with diabetes mellitus (DM) type I. Moreover, serum levels of C peptide and toxoplasma were determined by enzyme-linked immunosorbent assay. Glycosylated hemoglobin in blood was determined by colorimetry. Results Distribution of AA was higher in the case group (38.7%) compared with (18.7%) in the control group, whereas GG and AG were higher in the control group (45.3 and 36.0%, respectively) compared with (32.0 and 29.3%, respectively) in the case group. Regarding toxoplasma, it was more frequent in the case group (49.3%) compared with (30.7%) in the control group. The main risk factors of DM type I were high HbA1c [odds ratio (OR)= 10.7], positive toxoplasma finding (OR=4.7), high blood glucose (OR= 1.04), GG IL-10 polymorphism (OR=0.31), and low level of C peptide (OR=0.7). On the contrary, C peptide level and blood glucose were statistically significantly higher in positive toxoplasma cases (P<0.05). GG distribution was statistically significantly higher (P<0.001) in positive toxoplasma cases (48.6%) compared with (15.8%) in negative toxoplasma cases. The most significant predictors for G allele were positive toxoplasma result (OR=3.5) and high HbA1c level (OR=1.22). Conclusion GG genotype can no longer be viewed as a protective allele for DM type I, as higher IL-10 production with the ubiquitous nature of toxoplasma infection can lead to more pancreatic necrosis. The use of IL-10 as therapeutic cytokine for treatment of DM type I should be revised.

Genetic characterization of a patient with Cornelia de Lange syndrome with a novel NIPBL missense mutation Dalia F Hussen, Saida A Hammad, Ghada A Otaify, Alaaeldin G Fayez, Khaled M Refaat, Aya Elaidy, Mona S Aglan, Samia A Temtamy Middle East Journal of Medical Genetics 2020 9(1):24-29 Background Cornelia de Lange syndrome (CdLS) is a rare clinically and genetically heterogeneous disease. Cardinal phenotypic manifestations include specific dysmorphic facial features, growth retardation, intellectual disability, and upper limb anomalies. Mutations in five genes including NIPBL, SMC1A, SMC3, RAD21, and HDAC8 are known to be responsible for the syndrome, with the NIPBL gene mutation being the most prevalent (~80%). This study aimed to report the clinical, cytogenetic, and molecular characterization of a patient with CdLS with a heterozygous novel exonic missense mutation of the NIPBL gene. Patients and methods We have studied a male patient of 9 years and 4 months of age who presented with features suggestive of CdLS. Thorough clinical examination, conventional cytogenetic analysis, and molecular study using direct Sanger sequencing were performed. Results Clinical examination favored the diagnosis of CdLS. Conventional cytogenetic analysis revealed a normal 46, XY karyotype, with no evidence of premature sister chromatid separation. Molecular study showed a heterozygous novel exonic missense variant c. 2469G>T; p. (R657I) of the NIPBL gene. Conclusion A novel heterozygous exonic missense variant c. 2469G>T; p. (R657I) of the NIPBL gene was confirmed in our patient with CdLS. The phenotypic severity is probably correlated with the plausible effect of NIPBL gene mutation on the protein product rather than the variant type. The adverse effect of NIPBL gene mutation on the cohesion process mediated by cohesin complex is controversial.

One hundred years since Victor McKusick's birth: a tribute from Greece Christos S Bartsocas Middle East Journal of Medical Genetics 2020 9(1):30-34 Victor A. McKusick has been recognized as the world leading authority in medical genetics. Among his numerous achievements, we should point out his inspiration and the training of a large number of leading geneticists, OMIM, the 'Bar Harbor' courses, and his contribution to the Human Genome Project. Nonetheless, little is known of McKusick's active participation in genetic education of a large number of physicians worldwide. Greece is an example of his frequent presence there, always eager to friendly advice, assist, teach, and offer his vast knowledge and his unique and excellent personality and friendship to everyone around. Victor McKusick's relationship and experience with the Greek genetics community is briefly accounted.

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