To evaluate the nature and frequency of ATP-binding cassette subfamily B member 4 (ABCB4) gene variants in a series of French patients with intrahepatic cholestasis of pregnancy (ICP).
In this prospective study, the entire ABCB4 gene coding sequence was analysed by DNA sequencing in 50 unrelated women with ICP defined by pruritus and raised serum alanine aminotransferase activity or bile acid concentration, with recovery after delivery. Genomic variants detected in patients with ICP were sought in 107 control pregnant women. Patients with ICP and controls were of Caucasian origin.
Eight genomic variants were observed. One nonsense mutation (p.Arg144Stop) and two missense mutations (p.Ser320Phe and p.Thr775Met) were revealed each in one heterozygous patient. A third missense mutation (p.Arg590Gln) was detected in three heterozygous patients and in two homozygous patients also homozygous for a particular haplotype of three single-nucleotide polymorphisms (c.175C>T, c.504T>C, c.711A>T). The chromosomal frequency of the p.Arg590Gln variant was significantly different between the ICP and control group (7.0% vs 0.5%; p = 0.0017; OR 16.03, 95% CI 1.94 to 132.16). An association was also found between allele T of the c.504T>C silent nucleotide polymorphism and ICP (68.0% vs 53.7%; p = 0.017; OR 1.83, 95% CI 1.08 to 3.11). The chromosomal frequency of the p.Arg652Gly variant did not differ between the ICP and control group (p = 0.40).
This study shows that 16% of Caucasian patients with ICP bear ABCB4 gene mutations, and confirms the significant involvement of this gene in the pathogenesis of this complex disorder.
"Carriers of α-1-antitrypsin (AAT) deficiency can also be susceptible to COPD (Hersh et al., 2004; Poller et al., 1990). Interestingly, even such common traits as age-related macular degeneration (AMD) and carpal tunnel syndrome are associated with heterozygous carrier status for mutations in ABCA4, the gene responsible for Stargardt macular dystrophy (Bacq et al., 2009), and Charcot-Marie-Tooth neuropathy genes (Lupski et al., 2010), respectively (Figures 2C and 2D). In the latter case, haploinsufficiency due to either heterozygous SNV (Lupski et al., 2010) or heterozygous CNV (Del Colle et al., 2003) can convey the trait. "
[Show abstract][Hide abstract] ABSTRACT: Human diseases are caused by alleles that encompass the full range of variant types, from single-nucleotide changes to copy-number variants, and these variations span a broad frequency spectrum, from the very rare to the common. The picture emerging from analysis of whole-genome sequences, the 1000 Genomes Project pilot studies, and targeted genomic sequencing derived from very large sample sizes reveals an abundance of rare and private variants. One implication of this realization is that recent mutation may have a greater influence on disease susceptibility or protection than is conferred by variations that arose in distant ancestors.
[Show abstract][Hide abstract] ABSTRACT: The wavelet coefficients quantization model is suggested in this paper. Quantization is represented as addition of noise by equal parts in all bands of the wavelet transform. The linear approximation model of dependence of quantizing distortion power from a quantizing interval is considered. It is shown that use of the pointed model allows increased efficiency of picture coding.
Circuits and Systems for Communications, 2002. Proceedings. ICCSC '02. 1st IEEE International Conference on; 02/2002
[Show abstract][Hide abstract] ABSTRACT: Although most of popular application programs have online help, it is difficult for beginners to do what they want. This paper proposes a plain text help which is described using a programming language regarding a student as a computer - input from screen and output to mouse or keyboard. For example, menu ('F', 'S') denotes to select 'file (F)' from the main menu and 'save (S) ctrl+s' from the submenu. Functions wait ('Internet options') and continue() are used to move cursor to the 'Internet options' dialog box and to omit explanation. It is desirable to develop a translator from such a help to a hypertext help for supplementary information.
Proceedings - Frontiers in Education Conference 01/2004; DOI:10.1109/FIE.2004.1408793
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