Abstracts of the Second Conference of the Arab Association of Genetic Research (AAGR) Middle East Journal of Medical Genetics 2019 8(1):1-27

Prenatal counseling and diagnosis of Gaucher disease in Egypt: an 18-year experience Ahmed L Aboulnasr, Ekram M Fateen Middle East Journal of Medical Genetics 2019 8(1):28-32 Objective To provide prenatal counseling (PC) and prenatal diagnosis (PD) of Gaucher disease in pregnant women with previous affected sibling (s). Patients and methods PC was done in 154 pregnancies among 109 females from June 2000 to July 2018. Positive consanguinity was found in 98 (89.9%) couples. Chorionic villus sampling (CVS) was done between 11 and 12 weeks of gestational age in 115 pregnancies among 84 women. Two women had CVS in four pregnancies, five in three pregnancies, and 15 in two pregnancies. β-glucocerebrosidase activity was measured in chorionic villi. Results Of 154 pregnancies, 115 (74.68%) proceeded to CVS and 39 (25.32%) did not. Of the 39, 18 did not show up, eight already came late for PD, nine had missed or spontaneous abortion, three refused, and one had induced abortion before PD. In 110 (95.65%) pregnancies, enough chorionic villi were retrieved, and β-glucocerebrosidase was measured; 79 (71.82%) had normal enzyme activity and 31 (28.18%) had low activity. In five cases, we could not retrieve enough villi. Conclusion In spite of the presence of enzyme replacement therapy for Gaucher disease, it is not effective for all types, in addition to high cost and variable response. So, our responsibility in PC is to offer early diagnosis by CVS, as one of the options, to the pregnant women/couples.

Osteoarthritis in patients with familial Mediterranean fever: genetic basis and anti-inflammatory effect of laser acupuncture Manal M Thomas, Inas E. M Ahmed Kamel, Nagwa H Mohamed, Abeer Ramadan, Hala T El-Bassyouni Middle East Journal of Medical Genetics 2019 8(1):33-41 Background Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disease characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis, and renal amyloidosis. Arthritis could be the presenting symptom in many cases. Laser acupuncture has analgesic and anti-inflammatory effects on joint arthritis. Aim To highlight the genetic basis of osteoarthritis in patients with FMF and to highlight the anti-inflammatory effect of laser acupuncture on osteoarthritis of knee joint in Egyptian patients with FMF. Patients and methods A randomized controlled study was performed on 40 Egyptian patients with FMF. Molecular analysis of MEFV gene mutations was performed for all selected patients. Twenty patients with FMF were exposed to low-level laser acupuncture sessions (laser acupuncture group) and 20 other patients with FMF did not receive low-level laser acupuncture sessions (control group). Twelve low-level laser acupuncture sessions were implemented for the group treated with laser acupuncture three times per week for a duration of 4 weeks. All patients were checked before and after laser acupuncture sessions for pain intensity, radiography changes, and some inflammatory markers (white blood cell, eosinophils, lymphocytes, erythrocyte sedimentation rate, and C-reactive protein). Results M694V mutation was detected in 40% of patients. Patients with FMF with knee arthritis exposed to low-level laser acupuncture sessions showed significant improvement in pain intensity compared with the control group (P < 0.001). Statistical significance improvement of the treated knees started from the third follow-up laser session revealed by significant improvement in the radiography findings (P < 0.001). The inflammatory markers white blood cell, eosinophils, lymphocytes, erythrocyte sedimentation rate, and C-reactive protein became significantly lower (P = 0.037,P < 0.001,P < 0.001,P < 0.001, andP < 0.001, respectively). Conclusion M694V variant of MEFV gene is more frequent in the Egyptian patients with FMF with osteoarthritis. Low-level laser acupuncture therapy is effective in ameliorating pain of osteoarthritis in patients with FMF.

Body image, Anxiety, Depression and DNA damage in Obese Egyptian Women Moushira E Zaki, Hala T El-Bassyouni, Walaa Yousef, Ramy Mohamed, Safinaz El Toukhy, Samira Ismail Middle East Journal of Medical Genetics 2019 8(1):42-47 Background Obesity is a worldwide epidemic problem. Aim To investigate the role of obesity on body image, frequency of anxiety, depression disorders and DNA damage in a sample of Egyptian women. Methods The study included 172 women, 84 were obese and 88 were age-matched nonobese women. Results Obese women showed significant higher frequency of abnormal body image (77.4%) as compared with the nonobese (42%) (P< 0.0001). Moreover, they had significant higher frequencies of severe anxiety (26.2%) and depression (41.7%) than nonobese women (2.3 and 18.2%, respectively) (P < 0.001). Leukocyte DNA damage was evaluated by comet assay and revealed high DNA damage in obese women. Conclusion Obesity is a potential risk factor for abnormal body image, anxiety, depression, and DNA damage among Egyptian women. Identifying the psychological problems in obese women is essential to improve quality of life and promote management and prevention.

Chromosomal aberrations and chromosomal heteromorphisms among young couples with recurrent spontaneous abortion Dalia F Hussen, Saida A Hammad, Khaled M Refaat, Engy A Ashaat, Mona S Aglan, Ghada A Otaify, Hala T El-Bassyouni, Samia A Temtamy Middle East Journal of Medical Genetics 2019 8(1):48-54 Background Recurrent spontaneous abortion (RSA) is a common challenging reproductive problem, whereas the frequency of chromosomal abnormalities among couples with RSA varies from 2 to 8%. Chromosomal heteromorphisms that have been considered as normal variants are suspected to have a clinical effect in the form of infertility or RSA. Objective The objective of this research is to study the role and incidence of different types of chromosomal findings including chromosomal aberrations and chromosomal heteromorphisms among couples with RSA. The results can add to genetic counseling as well as can serve as a step for collecting national data concerning this issue. Patients and methods A total of 73 couples, comprising 146 cases with a history of RSA, have been enrolled in the study. All cases were subjected to full history taking, conventional cytogenetic analysis in addition to fluorescence in-situ hybridization technique whenever required. Results Among the studied cases (n = 146), 6.8% showed chromosomal abnormality. They were categorized into three (30%) cases with reciprocal translocation, four (40%) cases with Robertsonian translocation, two (20%) cases showed mosaic aneuploidy, and one (10%) case was chimera. Regarding chromosomal heteromorphisms, nine (6.16%) cases have been detected; the most frequent finding was pericentric inversion in chromosome 9 (inv (9)(p12q13)). Conclusion Before endeavoring any therapeutic intervention, couples who experience two or more abortions of unknown etiology should undergo a cytogenetic analysis, as RSA might be a rescuer mechanism to avoid distressing outcomes. Chromosomal heteromorphisms could be a contributing factor for RSA. Genetic counselors should pay attention to this issue until a conclusive mechanism can be verified.

A novel matrix metalloproteinase-2 mutation in two Egyptian siblings with Winchester syndrome Mona L Essawi, Heba A Hassan, Mona S Aglan, Samira Ismail, Samia A Temtamy Middle East Journal of Medical Genetics 2019 8(1):55-60 Background Winchester syndrome is one of multicentric osteolysis nodulosis and arthropathy spectrum, which is an autosomal recessive skeletal dysplasia. Homozygous or compound heterozygous mutations in matrix metalloproteinase-2 (MMP-2) gene are responsible for the condition. Approximately 21 mutations of MMP-2 gene have been reported to accompany multicentric osteolysis nodulosis and arthropathy. Patients and methods In this study, we report two Egyptian siblings diagnosed with Winchester syndrome based on clinical and radiological evaluation and confirmed by finding a novel homozygous mutation at exon 4 of MMP-2 gene by molecular studies. We also reviewed the literature for previously published patients with nonsense mutations of that gene. Results The detected MMP-2 mutation is the sixth reported nonsense mutation and the first pathogenic mutation detected in exon 4. Conclusion Phenotypic analysis of previously reported patients with different MMP-2 mutations including our present patients showed no genotype/phenotype correlation.

Frequency of balanced reciprocal translocations from couples with recurrent miscarriages correlates with the density of Alu and L1 repeat elements: literature finding-based study Fadel A Sharif Middle East Journal of Medical Genetics 2019 8(1):61-67 Background Balanced reciprocal translocations constitute the most frequently encountered structural chromosome abnormality in couples experiencing recurrent miscarriages. The present work was undertaken to assess the relation between reported reciprocal translocations and the density of Alu and L1 repetitive elements in the human chromosomes. Patients and methods Data analyzed were obtained from 55 relevant articles that investigated 98 054 individuals. The overall prevalence of reciprocal translocations reached 2.31% and was 1.65 times more frequent in the female patients. The 2262 (1402 in females and 860 in males) counted translocations were tested for association with Alu and L1 densities using Pearson's correlation test. Results A strong positive correlation (r = 0.87–0.89,P≤ 0.0001) was observed between the frequency of translocations and the densities of L1 and Alu in the human genome. Conclusion The results thus obtained reinforce the involvement of Alu and L1 DNA repeat elements in the generation of reciprocal translocations.