当前位置： SCI文献检索 > JOURNAL OF INHERITED METABOLIC DISEASE期刊下所有文献 > Marked geographic aggregation of acute intermittent porphyria families carrying mutation Q180X in Venezuelan populations, with description of further mutations.

Marked geographic aggregation of acute intermittent porphyria families carrying mutation Q180X in Venezuelan populations, with description of further mutations.

Abstract：

:Acute intermittent porphyria (AIP) caused by mutations in the hydroxymethylbilane synthase gene (HMBS), has been reported in almost all human populations, with varying frequencies. A founder effect for a few specific mutations in geographic regions where prevalence is high (Sweden, The Netherlands, Switzerland) has been established through haplotype analyses, while some other mutations (R26H, R26C) have been repeatedly reported in many populations with different genetic backgrounds. Epidemiological, biochemical and molecular data on AIP in Venezuela were gathered during the last two decades; 24 independent families with AIP were ascertained, based on a deficient HMBS activity and increased porphobilinogen (PBG) urinary excretion. Molecular analyses of coding and splicing regions were performed in 23 families, to establish disease-causing changes, and haplotype analyses were used to assess ancestral kinships between them. Changes were detected in 16 out of 23 families, 9 of them being different: R26H, R26C, c.87+5G>A, c.267-54_61delgaaggggt, R116W, Q180X, c.825+1G>A, c.913-1delG, and 3' UTR *277G>A. Seven mutations were found, each one in a single family; one mutation was present in two unrelated families, whereas mutation Q180X was shared by 7 independent kindreds, all of which had the same haplotype (-);T;A;T;G;T;A;G (3167delG; 3530T>C; 3581A>G; 3982T>C; 6479G>T; 7052T>C; 7064A>C; 7779G>A). Six out of seven different Q180X carrier families came from the same geographic focus (Santa Lucía, Miranda State). Dense geographic aggregation with one identical haplotype strongly suggests a remote founder phenomenon for these Venezuelan AIP families, carrying an unreported but most frequent mutation.

journal_name

J Inherit Metab Dis

journal_title

Journal of inherited metabolic disease

authors

Paradisi I,Arias S

doi

10.1007/s10545-010-9228-x

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

S455-63

eissn

0141-8955

issn

1573-2665

journal_volume

33 Suppl 3

pub_type

杂志文章

在线工具

Marked geographic aggregation of acute intermittent porphyria families carrying mutation Q180X in Venezuelan populations, with description of further mutations.