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Mutations in the PDE6A gene are known to cause a form of retinitis pigmentosa (RP43), characterized by progressive retinal degeneration. We describe an Emirati patient with RP caused by a novel mutation in PDE6A. Clinical diagnosis of RP was made based on clinical evaluation and electroretinograms. The molecular analysis involved performing whole-exome sequencing, which enabled the identification of a homozygous 2-bp deletion (c.1358_1359delAT) in PDE6A, which was predicted to result in a frameshift and premature termination (p.Ile452Serfs*7). The mutation completely removed the catalytic PDEase domain in the protein. The parents were found to be heterozygous carriers of the variant. We thus report the first known case of a pathological variant in the PDE6A gene from the Arabian Peninsula. [ABSTRACT FROM AUTHOR]

Aim Various studies incorporating Arab populations have reported on specific associations between HLA- DRB1 variants and rheumatoid arthritis ( RA). We sought to provide an overview on the association of HLA- DRB1 with RA in Arabs using meta-analysis tools. Methods Data on allele counts and frequencies were compiled from the relevant literature (published before 16 February 2016) and the associations of 13 - DRB1 variants with RA were assessed; relationships were defined in terms of odds ratios ( ORs) with a 95% confidence interval. Results Based on a collection of six studies, risk conferring or protective allele associations were derived from allele counts in 475 RA patients and 1213 controls. Two HLA- DRB1 alleles ( - DRB1*04, *10) significantly conferred an increased risk for RA (OR > 2; P < 0.0001). Conversely, four alleles ( -DRB1*03, *07, *11 and *13) significantly conferred a protective effect against RA (OR < 1; P < 0.05). No significant associations with RA were found for seven - DRB1 variants ( -DRB1*01, *08, *09, *12, *14, *15 and *16). Conclusion With increased statistical power and effect size over individual studies, we present a more robust profile on the association of HLA- DRB1 variants with RA in the Arab ethnicity, and contribute to the global geo-ethnic picture in this context. [ABSTRACT FROM AUTHOR]

Background/Aims: This study aimed to identify, clinically and molecularly, the causality of Rabson-Mendenhall syndrome in an Emirati family. It is one of the monogenic syndromes of abnormal glucose homeostasis, which result from insulin receptor defects. Methods: A novel nonsynonymous variant in the INSR gene was uncovered by whole exome sequencing and confirmed using Sanger sequencing in the patient and his parents. Various in silico tools were utilized to analyze the functional consequences of the variant. Results: Results revealed a previously unreported INSR variant in the family: c.421C>T (p.Arg141Trp). Homozygosity for the variant was found in the patient, while both parents were heterozygous. Conclusion: The nonsynonymous protein change hit a highly conserved arginine residue in the insulin-binding α-subunit of the receptor and was deemed 'functionally damaging' by a myriad of bioinformatics tools. This report is a step forward along the way of achieving a better molecular and clinical characterization of Rabson-Mendenhall syndrome. [ABSTRACT FROM AUTHOR]

Background: Small supernumerary marker chromosomes (sSMC) occur in 0.075% of unselected prenatal and in 0.044% of consecutively studied postnatal cases. Individuals with sSMC present with varying phenotype, ranging from normal to extremely mild or severe depending on the chromosomal region involved, the euchromatic content present and degree of mosaicism. Except for chromosomes 15 and 22, the number of reported cases of sSMC is extremely small to provide us with a good genotype-phenotype correlation. Analphoid sSMC are even rarer. To our knowledge only eight cases of analphoid inversion-duplication 3q sSMC are reported so far., Results: We describe here a one month old female child with several dysmorphic features and with a de novo analphoid supernumerary marker chromosome only in cultured skin fibroblast cells and not in lymphocytes. The marker was characterized as analphoid inversion-duplication 3q25.33-qter by oligo array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH) studies. The final skin fibroblast karyotype was interpreted as 47,XX,+der(3).ish inv dup(3)(qter-q25.33::q25.33-qter)(subtel 3q+,subtel 3q+) de novo., Conclusion: In addition to the eight reported cases of analphoid inversion-duplication 3q supernumerary marker in the literature, this is yet another case of 3q sSMC with a new breakpoint at 3q25.33 and with varying phenotype as described in the case report. Identification of more and more similar cases of analphoid inversion-duplication 3q marker will help in establishing a better genotype-phenotype correlation. The study further demonstrates that aCGH in conjunction with routine cytogenetics and FISH is very useful in precisely identifying and characterizing a marker chromosome, and more importantly help in providing with an accurate genetic diagnosis and better counseling to the family.

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).