BackgroundProgressive familial intrahepatic cholestasis (PFIC) is caused by variations in ATP8B1, ABCB11 or ABCB4 genes. Data on genetic variations in Indian patients with PFIC are lacking.MethodsCoding and splice regions of the three genes were sequenced in unrelated Indian children with PFIC phenotype. The variations identified were looked for in parents, 30 healthy persons and several variation databases, and their effect was assessed in-silico.ResultsAmong 25 children (aged 1–144 months), nine (36%) had unique major genomic variations (ATP8B1: 4, ABCB11: 3 and ABCB4: 2). Seven had homozygous variations, which were assessed as ‘pathogenic’ or ‘likely pathogenic’. These included: (i) four amino acid substitutions (ATP8B1: c.1660G > A/p.Asp554Asn and c.2941G > A/p.Glu981Lys; ABCB11: c.548 T > C/p.Met183Thr; ABCB4: c.431G > A/p.Arg144Gln); (ii) one 3-nucleotide deletion causing an amino acid deletion (ATP8B1: c.1587_1589delCTT/p.Phe529del); (iii) one single-nucleotide deletion leading to frame-shift and premature termination (ABCB11: c.1360delG/p.Val454Ter); and (iv) a complex inversion of 4 nucleotides with a single-nucleotide insertion leading to frame-shift and premature termination (ATP8B1: c.[589_592inv;592_593insA]/p.Gly197LeufsTer10). Two variations were found in heterozygous form: (i) a splice-site variation likely to cause abnormal splicing (ABCB11: c.784 + 1G > C), and (ii) a nucleotide substitution that created a premature stop codon (ABCB4: c.475C > T/p.Arg159Ter); these were considered as variations of uncertain significance. Three of the nine variations were novel.ConclusionsNine major genomic variations, including three novel ones, were identified in nearly one-third of Indian children with PFIC. No variation was identified in nearly two-thirds of patients, who may have been related to variations in promoter or intronic regions of the three PFIC genes, or in other bile-salt transport genes.Electronic supplementary materialThe online version of this article (10.1186/s12876-018-0835-6) contains supplementary material, which is available to authorized users.
Hepatitis B virus (HBV) has several genotypes. In the Indian population, genotypes A and D are the most frequent. HBV infection is hyper-endemic in the Lahaul and Spiti district in Himachal Pradesh; however, the virus genotype in this area is not known. We sequenced a 398-nucleotide segment of HBV genome that included parts of pre-S1/S2 and polymerase genes from 17 specimens from this district, and assigned a viral genotype to these. Of the 17 specimens studied, 13 (76% [95% confidence interval = 50-92%]) showed the presence of genotype C HBV; the remaining four were genotype D (n = 4; 24%) HBV. Prevalence of genotype C HBV was much higher in the district than in other parts of India. This may reflect the historical mixing of this population with that in China. Since genotype C has a higher risk of chronicity and mother-to-child transmission, prevention of HBV infection may need particular emphasis in this area.
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