Search

which results from an interplay between environmental and genetic factors. The latter can explain some of the geographic variability in T1D occurrence around the world. Of a particular importance in this regard are the HLA-DR, -DP and -DQ loci. Consequently, we aimed at elucidating the collective genetic profiles of various alleles relating to HLA-DRB1 and -DP in T1D patients throughout the Arab World using the tools of meta-analysis. As for HLA-DQA1 and DQB1 alleles; this analysis was completed and published previously (see Introduction). As a result of limited availability of relevant studies of the HLA-DP locus, only HLA-DRB1 alleles were tackled in this paper. Our study showed that significant increases in T1D risk resulted from harboring the alleles DRB1*03:01 and *04:05 (odds ratio 7.76 and 7.52, respectively). DRB1*04:01 and *04:02 were also predisposing for T1D in Arabs. Very strong evidence supported the protective effects of DRB1*10:01, *13:01, *15:02 and *16:01, with low heterogeneity and no publication bias. The results from the series of meta-analyses performed in this study help to complete the global genetic epidemiological map of T1D by providing statistically robust data from the Arab World. [ABSTRACT FROM AUTHOR]

Two common classes of deletions are described in the literature in individuals with Prader-Willi/Angelman syndrome (PWS/AS): one between breakpoint 1 (BP1) to BP3 and the other between BP2 to BP3 of the PWS/AS critical region on chromosome 15q11→q13. We present here a novel observation of an approximately 253-kb deletion between BP1 and BP2 on 15q11.2, in a 3½-year-old boy, who was referred to us with a clinical suspicion of having Angelman syndrome and presenting with mental retardation, neurological disorder, developmental delay and speech impairment. Karyotype and FISH results were found to be normal. The microdeletion between BP1 and BP2 includes four genes – NIPA1, NIPA2, CYFIP1 and TUBGCP5 which was detected by a high-resolution oligonucleotide array-CGH that was further validated by a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. The same deletion was observed in the father who presented with similar but relatively milder clinical features as compared to the affected son. Methylation studies by methylation-specific MLPA (MS-MLPA) of the SNRPN imprinting center (IC) showed a normal imprinting pattern, both in the patient and the father. To our knowledge a microdeletion limited only to the BP1-BP2 region has not yet been reported. The familial genetic alteration together with the striking clinical presentation in this study are interesting, but from our single case study it is difficult to suggest if the deletion is causative of some of the abnormal features or if it is a normal variant. The study however further strengthens the fact that genome-wide analysis by array CGH in individuals with developmental delay and mental retardation is very useful in detecting such hidden interstitial chromosomal rearrangements. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]