Medical Genetics

Updates about ethical, legal and psychological implications of genetic testing in newborns, children and adolescents Manal M Thomas Middle East Journal of Medical Genetics 2018 7(2):51-61 Genetic diseases affect physical and psychological health status and social well-being of patients and their families. For that reason, many organizations in the genetic field have published new guidelines on ethical and legal issues regarding genetic testing in children and adolescents. This review article aims to highlight the guidelines regarding quality standards of genetic testing in children and adolescents stressing on the ethical, legal and psychological implications of genetic testing. Specific guidelines on genetic testing and laws must be designed in Egypt to regulate genetic testing and enhance patients' rights putting specific legislations that comply with our traditions and beliefs. More knowledge and educational programs are recommended for health professionals and the public about measures to prevent diseases and promote health behaviors.

Genetic syndromes with immunological disturbances Iman Aly Helwa Middle East Journal of Medical Genetics 2018 7(2):62-77 Generally speaking, immunodeficiency conditions express a genetic component. In some of these cases, patients may request medical advice due to immune disturbance rather than due to genetic abnormality. Sometimes, the immune defect is not encountered in all cases. Yet, in certain cases, it is realized after diagnosis, while in others the immune defect is not the main clinical problem at all. However, immune defects maybe fatal in some syndromes and require urgent intervention. This review presents a brief overview on the immune response and then delineate the genetic syndromes manifesting immunological abnormalities.

Genome-editing technologies: Advancement, clinical applications, and ethical concerns Wessam E Sharaf-Eldin, Heba A Hassan, Nagham M El-Bagoury, Mona L Essawi Middle East Journal of Medical Genetics 2018 7(2):78-87 Genome editing is a powerful technology capable of precisely manipulating somatic and germline genomic sequences. The field is progressing at a rapid pace with unprecedented applications in biology and medicine. This systematic review represents a guide to different mechanisms, tools, and delivery systems used in genome editing. In addition, related ethical concerns are highlighted. So far, the most recent developed tool, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated enzyme, represents the most widely used approach owing to its simple application and enhanced efficiency. Hence, the major part of the review focuses on the clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated enzyme technology and its diverse applicability.

Corpus callosum abnormalities in 64 Egyptian patients: Neuropsychological and genetic studies Mahmoud Y Issa, Samira Ismail, Nivine Helmy, Alaa K Kamel, Sherine K Amin, Olweya M Abdel Baky, Maha S Zaki Middle East Journal of Medical Genetics 2018 7(2):88-95 Introduction Corpus callosum (CC) connects the left and right cerebral hemispheres. It is the largest white matter structure in the brain connecting mainly homotopic, as well as heterotopic, brain areas of both hemispheres. It has a major role in everyday behavior. Agenesis of CC can occur as isolated finding on MRI, or more commonly, it is associated with large number of brain anomalies. Patients and methods Neuropsychological and genetic assessment was done for 64 cases with corpus callosum abnormalities, whose age ranged from 6 months to 11 years and 9 months, with a mean age of 3 years and 6 months. This study was done from January 2012 till December 2014. Results Overall, 12.5% of the cases had chromosomal aberrations, 14% of the cases had identified genetic syndrome, and 73% of the cases were nonsyndromic/unclassified. Variable degrees of mental subnormality were encountered among 58 (92.2%) of 64 studied patients. Conclusion Abnormalities of the CC are often associated with cognitive deficits, autism, and epilepsy.

Mutation analysis of the arylsulfatase B gene among Egyptian patients with Maroteaux–Lamy disorder Mona L Essawi, Nagham M Elbagoury, Ola M Sayed, Mona S Aglan, Mona M Ibrahim, Hala N Soliman, Ekram M Fateen Middle East Journal of Medical Genetics 2018 7(2):96-103 Background Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) (OMIM: # 253200), is an autosomal recessive lysosomal storage disorder. It is caused by deficiency of the enzyme arylsulfatase B (ARSB), also known as N-acetylgalactosamine-4-sulfatase. ARSB is responsible for the degradation of the glycosaminoglycans dermatan sulfate and chondroitin 4-sulfate. Deficiency of the ARSB enzyme leads to accumulation of partially degraded dermatan sulfate in the lysosomes especially in connective tissues leading to clinical complications. Aim This study aimed at identifying the molecular basis of MPS VI (Mucopolysaccharidosis VI) among 15 Egyptian patients. Method Patients were from 15 families, age ranged from 1year and 5 months to 11 years and 9 months(5.19±0.8) with parental consanguinity in 11 families out of 15 (73.3%). All patients were subjected to all necessary clinical, radiological and biochemical assessments. Molecular assessment was carried out by sequencing the 8 coding exons of the ARSB gene for the fifteen studied patients. Results The disease causing mutations were revealed in 13 patients. Four novel mutations; c.257delA, c.189insA, p.Ser94Leu and p.Leu51Pro were identified as well as four previously reported mutations; p.Leu82Arg, p.Ser96Arg, p.Arg160X and p.Arg160Gln. Conclusion The study highlights the heterogeneity of the mutational pattern which was obvious in finding novel mutations in homozygous forms in approximately 40% of the studied patients. Exons 1 and 2 seem to carry most of the mutations in the Egyptian MPS VI patients. Arginine at position 160 seems to be the most abundant mutational hot spot in the Egyptian MPS VI patients.

Assessment of serum level of vitamin D in infants and children with Down syndrome Manal M El-Hawary, Shahira M El-Shafie, Heba El-Awady, Tamer Ragab, Raooth Nabile Middle East Journal of Medical Genetics 2018 7(2):104-111 Background Vitamin D has multiple extraskeletal functions. Patients with Down syndrome (DS) are at more risk of vitamin D deficiency owing to multiple environmental and hormonal factors, so vitamin D supplementation plays a vital role in their lifestyle. Objective The aim of the study is to assess serum vitamin D level and to study the several factors that may affect its level in infants and children with DS. Patients and methods The study enrolled 50 children, where 30 of them were diagnosed as having DS (group I) and the other 20 were defined as a control group (group II). Detailed systemic examination was performed for all participants. Anthropometric measurements including weight, height, and head circumference were assessed. Blood samples were collected and evaluated for 25-hydroxy vitamin D level. Results The mean serum vitamin D level was 30.65 ± 20.64 in group I compared with 55.80 ± 22.79 in group II, with significant P value of less than 0.0001. In patients with DS, 6.7% were severely deficient (<10 ng/ml), 53.3% had insufficient serum vitamin D level (10–32 ng/ml), and 40% had adequate serum vitamin D level (>32 ng/ml). In group II, only 20% had insufficient serum vitamin D level and 80% had adequate level. Conclusion Vitamin D deficiency and insufficiency were more prevalent in patients with DS. Vitamin D insufficiency was also reported in the control group, which indicates that it is a common health problem even among healthy participants. Diet rich in vitamin D, adequate sun exposure, and vitamin D supplements prevent vitamin D deficiency.

Dysregulation of tumor necrosis factor-α and interleukin-6 as predictors of gestational disorders Hala T El-Bassyouni, Sahar M Abdel Raouf, Mona K Farag, Wasela M Nawito, Tarek M Salman, Khaled R Gaber Middle East Journal of Medical Genetics 2018 7(2):112-117 Background Approximately 7% of all pregnancies are complicated by gestational diabetes mellitus (GDM). Maternal complications pertaining to GDM are associated with a variety of complications in pregnancy, most notably preeclampsia (PE), which is characterized by an exaggerated systemic inflammatory response. The study aimed to examine the clinical significance of detection of the cytokine tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in pregnant women with GDM and PE. Patients and methods A total of 60 pregnant women, comprising 25 diagnosed with GDM, 15 with PE, and 20 controls normoglycemic and normotensive, were examined. TNF-α and IL-6 were estimated. Results IL-6 concentration was significantly higher in the pregnant females who developed GDM and PE later during pregnancy compared with the control group (P < 0.0001 and 0.003, respectively). TNF-α concentration showed only significant difference in the women who developed GDM later during pregnancy when compared with the control group (P < 0.0001). Conclusion TNF-α and IL-6 have been proposed to play an important role in the prediction of the pathogenesis of GDM and PE.

Genetic study of the association of specific language impairment to markers near FOXP2 gene Mohammed M Sayed-Ahmed, Samira Ismail, Alia M El-Shoubary, Mona L Essawi, Moushira E Zaki, Ahmed N Khattab Middle East Journal of Medical Genetics 2018 7(2):118-123 Background One important language gene is FOXP2, a mutation of which affects language and speech in relatively rare and severe forms. However, certain genetic markers adjacent to FOXP2 gene are highly suspected to be involved in common forms of specific language impairment (SLI). Identification of these genetic loci related to SLI may yield new insights into its causes, along with improved diagnosis, and treatment. Aim of the work To study the association of SLI to two genetic markers residing near FOXP2 gene, namely, the repeat unit GATA of D7S3052 marker and GATT tetranucleotide repeats in intron 6 of CFTR gene. Patients and methods The current study included 50 children with SLI and 50 normal controls, aged 3–8 years. All participants were subjected to genetic molecular association study as well as detailed protocol of assessment including full history and examination, and evaluation of language skills and mental ability (intelligence quotient). Results There was no difference between the SLI and normal groups regarding molecular results of GATT repeats of CFTR gene, and there was a nonsignificant difference regarding results of GATA repeats of D7S3052 marker (P > 0.05). Conclusion The association of SLI with D7S3052 marker near FOXP2 gene in current study is statistically nonsignificant. However, a statistical significance of this association could be expected with a larger number of cases, more diversity of SLI types and degrees, and more comprehensive procedures.

MicroRNA-mediated sensitization of lung cancer cells to chemotherapeutics: the roles of miR-21 and miR-155 Nnaemeka D Ndodo, Barnabas Danborno, Samuel S Adebisi Middle East Journal of Medical Genetics 2018 7(2):124-131 Background MicroRNAs (miRNAs) are conserved short 22-nucleotide RNAs with important roles in regulating gene expression. Misregulation of genes that control cell-cycle and cell-fate determination often contributes to cancer. The aims of this work were to evaluate the expressions of two oncogenic miRNA (oncomiRs), miR-21 and miR-155, in lung cancer, and to see whether reintroduction or inhibition of these would affect progression or aid sensitivities of the lung cancer cells to major chemotherapeutics. Methods This work involved cell culture of lung adenocarcinoma cells H358 and A549 and normal lung cells. It compared the miRNA expression profiles of two miRNAs (miR-21 and miR-155) in cancer and normal lung cell lines using real-time PCR and then treated with three known chemotherapeutics, namely cisplatin, etoposide and paclitaxel, and concluded by inhibiting overexpressed miRNA by transfecting the cancer cells with miRNA inhibitors, and proliferation was measured with sulforhodamine-B assay. Results showed that miR-21 was overexpressed in the entire cell lines used, which is consistent with the role of miR-21 as an oncomir, whereas miR-155 was downregulated, suggesting that miR-155 could be acting as a tumor suppressor. Furthermore, inhibition of miR-21 function in H358 lines using 50 nM Ambion anti-miR led to a decreased proliferation of H358 cells compared with the 50 nM anti-miR-155-treated group. Downregulation of miR-21 seems to sensitize lung cancer cells to chemotherapeutics (etoposide). Conclusion This work demonstrated that miR-21 at 50 nM might sensitize lung cancer cells to chemotherapeutics (etoposide) and that miR-155, a known oncogenic miRNA, seems to be acting as a tumor suppressor in lung cancer, which promises to be of immense therapeutic importance.

Fragile X syndrome: diagnosis by molecular characterization of FMR1 gene and clinical correlation Hoda M Abd El-Ghany, Eman A Ehssan, Menatalla K El-Deen, Rasha A Al-Gamal, Rania M Samy, Amany S El-Deen Middle East Journal of Medical Genetics 2018 7(2):132-138 Background One of the most common forms of inherited intellectual disability (ID) is fragile X syndrome (FXS), which is caused by expansion of cytosine–guanine–guanine trinucleotide repeat at the 5′ untranslated region of the fragile X mental retardation gene (FMR1) at Xq27. The cytosine–guanine–guanine repeat expansion leads to hypermethylation and inactive transcription of the gene. The present study aimed to detect expected FMR1 gene alleles by methylation-sensitive PCR and its clinical correlation for rapid screening of FXS among male patients with ID. Patients and methods The study included 50 male patients with ID and clinical features suggestive of FXS, who were compared with 50 healthy age-matched volunteers. All patients were subjected to full history taking, thorough clinical examination using a 15-item checklist [physical (big ears, joint hyperextensibility, Simian crease, wide forehead, macroorchidism, and elongated face) and neurological features (mental retardation, family history of mental retardation, poor eye contact, hand biting, hyperactivity, perservative speech, tactile defensiveness, hand flapping, and short attention span)], and karyotyping using GTG banding. Methylation-sensitive PCR technique after bisulfite treatment of DNA was applied for the detection of expanded alleles of the FMR1 gene. Results Clinical score in patients with abnormal alleles was significantly higher compared with patients with normal alleles. GTG-banding technique showed normal 46XY male karyotype for studied patients. Frequency of normal FMR1 gene alleles was detected in the control group (100%) and 44 (88%) patients. Abnormal alleles were detected in six (12%) patients: three (6%) patients with full mutation (FM) and three (6%) patients with premutation carrier. Conclusion Our study revealed that PCR-positive results of fragile X correlate with the checklist clinical score rather than a single clinical entity.