Two new polymorphisms in introns 2 and 3 of the human porphobilinogen deaminase gene

Daimon, Makoto; Morita, Yoshihiro; Yamatani, Keiichi; Inamori, Masahiko; Fukase, Norio; Ohnuma, Hiroshi; Sakamoto, Kazuhiko; Ogawa, Atsushi; Manaka, Hideo; Tominaga, Makoto; Sasaki, Hideo

doi:10.1007/bf00219676

Cited by 5 publications

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“…The PBGD, or HMBS, gene has been mainly studied in white Caucasian populations; it contains 15 exons spread over 10 kb on chromosome 11q24.1-24.2 (Yoo et al 1993). To date, over 165 mutations that cause AIP have been identified (Grandchamp 1998 for review; Whatley et al 1999) and in the Caucasian population, 14 intragenic single nucleotide polymorphisms (SNPs) have been identified in the PBGD gene (Lee and Anvret 1987;Llewellyn et al 1987;Lee et al 1988;Gu et al 1991;Lee 1991;Daimon et al 1993;Yoo et al 1993;Law et al 1999;Whatley et al 1999). Two SNPs have been identified in the nonerythroid promoter region (Picat et al 1991;Schreiber et al 1992;Lundin and Anvret 1997).…”

Section: Introductionmentioning

confidence: 95%

Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms

et al. 2000

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Acute intermittent porphyria (AIP), the most common acute hepatic porphyria, is a low-penetrant autosomal dominant disorder caused by mutations in the porphobilinogen deaminase (PBGD) or hydroxymethylbilane synthase (HMBS) gene. Although AIP has been identified in all the main ethnic groups, little is known about PBGD gene defects in Africans, Afro-Caribbean and Afro-Americans. We have carried out PBGD gene screening among seven unrelated AIP families and 98 controls belonging to the Afro-Caribbean (French West Indies) and the sub-Saharan African (Morocco, Algeria, Cameroon, Mali, and Burkina Faso) populations. Using denaturing-gradient gel electrophoresis (DGGE) and direct sequencing we characterized six different mutations, including four novel, from the seven AIP families: three splicing defects (IVS 5+2 Ins G; IVS 7+1 G to A in two families; IVS 10-1 G to T); a small deletion (1004 Del G); and two missense mutations (R116 W; A270G). The allele frequencies of the 14 polymorphic sites, previously known in the normal Caucasian population, were similar in Africans and Afro-Caribbean control populations. Interestingly, two common new intragenic polymorphic sites, close to intron/junction boundaries, were identified only in blacks: 1) in intron 2, a single base-pair G deletion at position 3167 (G:0.88; delG:0.12); 2) in intron 10, a A/G dimorphism at position 7052 (A:0.56; G:0.44). These two single nucleotide polymorphisms (SNPs) were never encountered in 750 unrelated Caucasian subjects. The allele frequency distributions of populations within black ethnic groups (Africans and Afro-Caribbean) are similar. This study highlights differences both in PBGD gene mutations causing AIP and in SNPs between white and black peoples; the allele frequencies provided contribute to a better knowledge of the variability of these markers among the major population groups, especially in sub-Saharan West African and Afro-Caribbean populations.

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Section: Introductionmentioning

confidence: 95%

Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms

et al. 2000

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“…However, mutations W198X and R116W have been detected in a large number of Swedish and Dutch AIP families, respectively (33,40). In addition, a variety of intragenic RFLPs have been identified which have proven useful for heterozygote diagnosis in informative families whose mutations have not been determined (42)(43)(44)(45)(46)(47)(48). However, there is marked linkage disequilibrium for the intron 1 and intron 3 RFLPs in northern European and American populations (49)(50)(51), with the exception of a recently identified common intron 10 Hinfl site (10).…”

Section: Introductionmentioning

confidence: 99%

Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme.

et al. 1994

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Detection of DNA variations in the polymorphic hydroxymethylbilane synthase gene by high-resolution melting analysis

Ulbrichova-Douderova

Martásek

2009

Analytical Biochemistry

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Two new polymorphisms in introns 2 and 3 of the human porphobilinogen deaminase gene

Abstract: Sequencing of the polymerase chain reaction amplified exon 2-4 fragment of the human porphobilinogen deaminase gene revealed a G/T polymorphism (I2G and I2T) in intron 2, and a G/A polymorphism (I3G and I3A) in intron 3 of the gene. The frequencies of these alleles are presented.

Cited by 5 publications

References 5 publications

Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms

Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms

Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme.

Detection of DNA variations in the polymorphic hydroxymethylbilane synthase gene by high-resolution melting analysis

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