Abstract: Hepatocellular carcinoma (HCC) is a preventable disease rather than a curable one, since there is no well-documented effective treatment modality until now, making the molecular study of this disease mandatory. We studied gene expression profile of 17 Egyptian HCC patients associated with HCV genotype-4 infection by c-DNA microarray. Out of the 15,660 studied genes, 446 were differentially expressed; 180 of them were up regulated and 134 were down regulated. Seventeen genes out of the 180 up-regulated genes are involved in 28 different pathways. Protein phosphatase 3 (PPP3R1) is involved in 10 different pathways followed by fibroblast growth factor receptor 1 (FGFR1), Cas-Br-M ecotropic retroviral transforming sequence b (CBLB), spleen tyrosine kinase (SYK) involved in three pathways; bone morphogenetic protein 8a (BMP8A), laminin alpha 3 (LAMA3), cell division cycle 23 (CDC23) involved in 2 pathways and NOTCH4 which regulate Notch signaling pathway. On the other hand, 25 out of the 134 down-regulated genes are involved in 20 different pathways. Integrin alpha V alpha polypeptide antigen CD51 (ITGVA) is involved in 4 pathways followed by lymphotoxin alpha (TNF superfamily, member 1) (LTA) involved in 3 pathways and alpha-2-macroglobulin (A2M), phosphorylase kinase alpha 2-liver (PHKA2) and MAGI1 membrane associated guanylate kinase 1 (MAGI1) involved in 2 pathways. In addition, 22 genes showed significantly differential expression between HCC cases with cirrhosis and without cirrhosis. Confirmation analysis was performed on subsets of these genes by RT-PCR, including some up-regulated genes such as CDK4, Bax, NOTCH4 and some down-regulated genes such as ISGF3G, TNF, and VISA. This is the first preliminary study on gene expression profile in Egyptian HCC patients associated with HCV-Genotype-4 using the cDNA microarray. The identified genes could provide a new gate for prognostic and diagnostic markers for HCC associated with HCV. They could also be used to identify candidate genes for molecular target therapy.

Abstract: Interstitial deletions of the proximal long arm of chromosome 3 are very rare and a defined clinical phenotype is not established yet. We report on the clinical, cytogenetic and molecular findings of a 20-month-old Hispanic male with a 2.5 Mb de novo deletion on q13.11q13.12. Up to now, this is the smallest deletion reported among patients with the proximal 3q microdeletion syndrome. The patient has distinct facial features including brachycephaly, broad and prominent forehead, flat nasal bridge, prominent ears, anteverted nose, tetralogy of Fallot, bilateral cryptorchidism, and peripheral skeletal abnormalities. To further delineate the proximal 3q deletion syndrome, the phenotype of our patient was compared with 10 other patients previously described. We found that ALCAM and CBLB are the only genes deleted in our patient and based on previously published data, we propose that the CBLB gene is responsible for the craniofacial phenotype in patients with deletions of proximal 3q region.

Abstract: To clarify the contribution of Cblb to the development of type1 diabetes (T1D), we investigated Japanese younger-onset T1D patients. We sequenced the cblb gene in 10 T1D patients and screened the identified mutations in 109 Japanese T1D patients and 100 normal subjects. In addition to four previously reported synonymous single nucleotide polymorphisms (SNPs), we identified two novel nonsynonymous variants (786 C>T (A155V) and 1718 A>G (N466D)). The A155V mutation was found in one subject with Basedow's disease whose mother also carried both the mutation and Basedow's disease. The N466D mutation was found in 6 T1D cases including a subject who was classified as fulminant T1D. We found no significant differences in the allele frequency of these SNPs among T1D and control subjects, suggesting that the contribution of cblb to the genetic susceptibility to T1D might not be high for Japanese younger-onset T1D.

Abstract: Interstitial deletions of the proximal long arm of chromo-some 3 are very rare and a defined clinical phenotype is notestablished yet. We report on the clinical, cytogenetic andmolecular findings of a 20-month-old Hispanic male with a2.5 Mb de novo deletion on q13.11q13.12. Up to now, this isthe smallest deletion reported among patients with theproximal 3q microdeletion syndrome. The patient hasdistinct facial features including brachycephaly, broad andprominent forehead, flat nasal bridge, prominent ears,anteverted nose, tetralogy of Fallot, bilateral cryptorchidism,and peripheral skeletal abnormalities. To further delineatethe proximal 3q deletion syndrome, the phenotype of ourpatient was compared with 10 other patients previouslydescribed. We found that ALCAM and CBLB are the onlygenes deleted in our patient and based on previouslypublished data, we propose that the CBLB gene isresponsible for the craniofacial phenotype in patients withdeletions of proximal 3q region.

Abstract: Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real-time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA forms mut (n = 19), cblA (n = 9) and cblB (n = 4). All the mut 0 and some of the cblB patients had the most severe clinical and biochemical manifestations, displaying non-inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl) in vitro and high plasma odd-numbered long-chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast, mut − and cblA patients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in the MUT gene, including mut 0 and mut − changes, affected mRNA stability. A new sequence variation (c.562G>C) in the MMAA gene was identified. Most of the cblA patients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense-mediated decay (NMD).