Genomics into Healthcare: the 5th Pan Arab Human Genetics Conference and 2013 Golden Helix Symposium.

The joint 5th Pan Arab Human Genetics conference and 2013 Golden Helix Symposium, "Genomics into Healthcare" was coorganized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in collaboration with the Golden Helix Foundation (http://www.goldenhelix.org) in Dubai, United Arab Emirates from 17 to 19 November, 2013. The meeting was attended by over 900 participants, doctors and biomedical students from over 50 countries and was organized into a series of nine themed sessions that covered cancer genomics and epigenetics, genomic and epigenetic studies, genomics of blood and metabolic disorders, cytogenetic diagnosis and molecular profiling, next-generation sequencing, consanguinity and hereditary diseases, clinical genomics, clinical applications of pharmacogenomics, and genomics in public health.

Hidradenitis suppurativa (or Acne inversa) with autosomal dominant inheritance is not linked to chromosome 1p21.1-1q25.3 region.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by swollen, painful, inflamed lesions in the axillae, groin, armpits and other parts of the body that contain apocrine glands. The aetiology of HS is unknown, and earlier reports indicate genetic locus responsible for this phenotype on chromosome 1p21.1-1q25.3, but no causative gene(s) have yet been identified. We studied two large multigeneration pedigrees (UR251 and UR252), in which the condition appeared to segregate as an autosomal dominant trait with 100% penetrance. No skipping of generations was observed in either family. Pedigrees consist of 96 individuals, including 25 affected individuals. Because of squamous cell carcinoma, a few deaths were reported in family UR0251. The locus on chromosome 1p21.1-1p25.3, known from previous studies is associated with HS, was excluded in both families by linkage and haplotype analyses. Further studies are in progress to identify the region that is associated with the phenotype in these families.

Consanguinity and reproductive health among Arabs.

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity.

Erythropoietin to augment myocardial salvage induced by coronary thrombolysis in patients with ST segment elevation acute myocardial infarction.

To determine whether the administration of erythropoietin (EPO) early after the onset of ischemia could enhance the preservation of jeopardized myocardium by reperfusion, 236 patients admitted <6 hours after the onset of chest pain indicative of acute coronary syndromes confirmed to be ST-segment elevation acute myocardial infarctions who were treated with tenecteplase to induce coronary thrombolysis were studied. Patients were randomized to standard care or standard care plus the administration of a single dose of EPO 30,000 IU intravenously immediately before the onset of treatment with tenecteplase. The primary end point was enzymatically estimated infarct size. The results indicated that infarct size index was virtually identical in the 2 groups, with a mean +/- SE of 13.2 +/- 0.1 creatine kinase-MB gram equivalents in controls and 12.4 +/- 0.9 creatine kinase-MB gram equivalents in patients treated with EPO. In conclusion, although the early administration of EPO was apparently safe, it did not enhance the preservation of jeopardized ischemic myocardium.

Clinical presentation and outcomes of acute coronary syndromes in the gulf registry of acute coronary events (Gulf RACE).

OBJECTIVE: To identify the characteristics, treatments and hospital outcomes for patients diagnosed with acute coronary syndromes (ACS) in the Gulf area. METHODS: Prospective, multinational, multicentre, observational survey of consecutive ACS patients who were admitted to 65 hospitals during May 2006. RESULTS: A total of 1484 ACS patients were recruited. The mean age was 55 years, and 76% were men. The final discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 37%, non-ST-segment elevation myocardial infarction (NSTEMI) in 32%, left bundle branch block myocardial infarction (LBBB MI) in 2%, and unstable angina in 29%. Among patients with STEMI and LBBB MI, the reperfusion rate was 65%, with use of primary percutaneous coronary intervention in 7% and thrombolytic therapy in 93%. When thrombolytic therapy was used, the median door to needle time was 45 minutes, with 37% receiving it within 30 minutes of hospital presentation. During the first day of hospitalization, aspirin was administered to 94%, clopidogrel to 51%, and beta blockers to 65%. Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers and statins were used in 62% and 82%, respectively. Coronary angiography during hospitalization was performed in 21%. In-hospital mortality was 3%. CONCLUSION: We were able to determine the characteristics, treatments and in-hospital outcomes of patients hospitalized with ACS in our region. There is room for improvement in using medications, reducing needle to door time and utilizing more cardiac catheterization services.

Genomewide linkage scan for split-hand/foot malformation with long-bone deficiency in a large Arab family identifies two novel susceptibility loci on chromosomes 1q42.2-q43 and 6q14.1.

Split-hand/foot malformation with long-bone deficiency (SHFLD) is a rare, severe limb deformity characterized by tibia aplasia with or without split-hand/split-foot deformity. Identification of genetic susceptibility loci for SHFLD has been unsuccessful because of its rare incidence, variable phenotypic expression and associated anomalies, and uncertain inheritance pattern. SHFLD is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has also been postulated. We conducted a genomewide linkage analysis, using a 10K SNP array in a large consanguineous family (UR078) from the United Arab Emirates (UAE) who had disease transmission consistent with an autosomal dominant inheritance pattern. The study identified two novel SHFLD susceptibility loci at 1q42.2-q43 (nonparametric linkage [NPL] 9.8, P=.000065) and 6q14.1 (NPL 7.12, P=.000897). These results were also supported by multipoint parametric linkage analysis. Maximum multipoint LOD scores of 3.20 and 3.78 were detected for genomic locations 1q42.2-43 and 6q14.1, respectively, with the use of an autosomal dominant mode of inheritance with reduced penetrance. Haplotype analysis with informative crossovers enabled mapping of the SHFLD loci to a region of approximately 18.38 cM (8.4 Mb) between single-nucleotide polymorphisms rs1124110 and rs535043 on 1q42.2-q43 and to a region of approximately 1.96 cM (4.1 Mb) between rs623155 and rs1547251 on 6q14.1. The study identified two novel loci for the SHFLD phenotype in this UAE family.

Ectrodactyly with aplasia of long bones (OMIM; 119100) in a large inbred Arab family with an apparent autosomal dominant inheritance and reduced penetrance: clinical and genetic analysis.

Ectrodactyly with aplasia of long bones syndrome is one of the most recognizable defects involving the extremities. We have studied a very large eight-generation consanguineous Arab family from the United Arab Emirates (UAE) with multiple severe limb anomalies resembling this condition (OMIM; 119100), for which the affected gene is unknown. The pedigree consists of 145 individuals including 23 affected (14 males/9 females) with limb anomalies. Of these, 18 had tibial aplasia (TA) usually on the right side. The expression of the phenotype was variable and ranged from bilateral to unilateral TA with ectrodactyly and other defects of the extremities. The mode of inheritance appears to be autosomal dominant with reduced penetrance. There were 10 consanguineous marriages observed in this pedigree. This could suggest possible pseudodominance due to high frequency of the mutant allele. Candidate loci for the described syndrome include GLI3 (OMIM: 165240) on 7p13, sonic hedgehog; (OMIM: 600725) on 7q36, Langer-Giedion syndrome (OMIM: 150230) on 8q24.1 and split-hand/foot malformation 3 (OMIM: 600095) on 10q24. In addition, bilateral tibial hemimelia and unilateral absence of the ulna was previously observed to co-segregate with deletion of 8q24.1. Two-point linkage and haplotype analyses did not show the involvement of the above regions in this family.

CTGA: the database for genetic disorders in Arab populations.

The Arabs comprise a genetically heterogeneous group that resulted from the admixture of different populations throughout history. They share many common characteristics responsible for a considerable proportion of perinatal and neonatal mortalities. To this end, the Centre for Arab Genomic Studies (CAGS) launched a pilot project to construct the 'Catalogue of Transmission Genetics in Arabs' (CTGA) database for genetic disorders in Arabs. Information in CTGA is drawn from published research and mined hospital records. The database offers web-based basic and advanced search approaches. In either case, the final search result is a detailed HTML record that includes text-, URL- and graphic-based fields. At present, CTGA hosts entries for 692 phenotypes and 235 related genes described in Arab individuals. Of these, 213 phenotypic descriptions and 22 related genes were observed in the Arab population of the United Arab Emirates (UAE). These results emphasize the role of CTGA as an essential tool to promote scientific research on genetic disorders in the region. The priority of CTGA is to provide timely information on the occurrence of genetic disorders in Arab individuals. It is anticipated that data from Arab countries other than the UAE will be exhaustively searched and incorporated in CTGA (http://www.cags.org.ae).

Assessment of coronary bypass graft patency by electron-beam computed tomography.

Twenty-one patients undergoing coronary artery bypass grafting were prospectively evaluated by conventional selective coronary angiography and electron-beam computed tomography. Eighty bypass grafts (60 saphenous vein and 20 left or right internal mammary artery) were evaluated for patency. The sensitivity and specificity of electron-beam computed tomography were 72% and 100%, respectively; positive and negative predictive values were 100% and 92.5%, respectively. Sensitivity and specificity according to coronary region were: left anterior descending artery, 33% and 100%; diagonal artery, 67% and 100%; circumflex artery, 75% and 100%; right coronary artery, 100% and 100%. Electron-beam computed tomography is relatively accurate and a promising tool for noninvasive evaluation of graft patency after coronary artery bypass graft surgery.