Acute intermittent porphyria: Characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G&gt;T)

Siervi, Adriana De; Méndez, Manuel; Parera, Victoria Estela; Varela, Laura Sabina; Batlle, Alcira; Rossetti, María Victoria

doi:10.1002/(sici)1098-1004(199910)14:4<355::aid-humu19>3.0.co;2-t

Cited by 11 publications

(8 citation statements)

References 9 publications

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“…One of the splice site mutations is located in the −2 position of the acceptor splice site of intron 8 (c.423-2A>G, GENBANK HM856802) leading to the in-frame deletion of 15 bp ( Figure 1 ). The same result has been found for a point mutation in the last base of intron 8 already described for another Argentinean family [ 34 ].…”

Section: Discussionsupporting

confidence: 86%

“…At present 177 AIP families (299 affected individuals) were diagnosed at CIPYP. Of them, 107 were also studied at molecular level and results for 48 families were already described [ 7 , 28 , 29 , 34 ]. In the last 10 years 58 new families were also biochemically diagnosed as AIP and molecular analysis revealed 19 mutations, 4 new and 15 already reported of which 7 were described for the first time in our population ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

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Acute Intermittent Porphyria in Argentina: An Update

Cerbino

Gerez

Varela

et al. 2015

BioMed Research International

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Porphyrias are a group of metabolic diseases that arise from deficiencies in the heme biosynthetic pathway. A partial deficiency in hydroxymethylbilane synthase (HMBS) produces a hepatic disorder named Acute Intermittent Porphyria (AIP); the acute porphyria is more frequent in Argentina. In this paper we review the results obtained for 101 Argentinean AIP families and 6 AIP families from foreign neighbour countries studied at molecular level at Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP). Thirty-five different mutations were found, of which 14 were described for the first time in our population. The most prevalent type of mutations was the missense mutations (43%) followed by splice defects (26%) and small deletions (20%). An odd case of a double heterozygous presentation of AIP in a foreign family from Paraguay is discussed. Moreover, it can be noted that 38 new families were found carrying the most frequent mutation in Argentina (p.G111R), increasing to 55.66% the prevalence of this genetic change in our population and adding further support to our previous hypothesis of a founder effect for this mutation in Argentina. Identification of patients with an overt AIP is important because treatment depends on an accurate diagnosis, but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death.

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Section: Discussionsupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Acute Intermittent Porphyria in Argentina: An Update

Cerbino

Gerez

Varela

et al. 2015

BioMed Research International

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“…From each patient, genomic DNA isolation, PCR's reactions including all the PPOX coding exons and sequencing reactions were made using the methodology already described (De Siervi et al 1999;2000).…”

Section: Dna Isolation Amplification and Sequencing Reactionsmentioning

confidence: 99%

Two new mutations (H106P and L178V) in the protoporphyrinogen oxidase gene in Argentinean patients with variegate porphyria

et al. 2000

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“…Molecular analysis of the HMBS gene has so far revealed more than 160 mutations among AIP patients, with wide molecular heterogeneity despite a relatively uniform clinical outcome (for review, see Grandchamp 1998). Clusters of mutations have been reported in different regions such as Sweden (Lee et al 1991) and Argentina (De Siervi et al 1999a, De Siervi et al 1999b), although most have been detected only in single families. Large heterogeneity of AIP mutations has been reported in Finland (Kauppinen et al 1995), France (Puy et al 1997), The Netherlands (Gu et al 1993), United Kingdom (Whatley et al 1999) and North America (Petersen et al 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Large heterogeneity of AIP mutations has been reported in Finland (Kauppinen et al 1995), France (Puy et al 1997), The Netherlands (Gu et al 1993), United Kingdom (Whatley et al 1999) and North America (Petersen et al 1998). Few data are available for countries of the Mediterranean area (De Siervi et al 1999a, De Siervi et al 1999b) and no studies have been conducted on the Italian population.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of the hydroxymethylbilane synthase (HMBS) gene in Italian patients with acute intermittent porphyria: Report of four novel mutations

et al. 2000

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Acute intermittent porphyria (AIP) is an autosomal disorder caused by molecular abnormalities in the hydroxymethylbilane synthase (HMBS) gene coding for the third enzyme in the heme biosynthetic pathway. So far, more than 160 different mutations responsible for AIP have been identified in this gene. We have now identified seven mutations in eight unrelated Italian patients with AIP: two splicing defects (IVS7+2T→C, 612G→T), three small deletions (308‐309delTG, 730‐731delCT, 182delA) and two missense mutations (134C→A, 541C→T). The splicing defects were responsible for activation of splicing cryptic sites respectively within intron 7 (15 bp insertion) and exon 10 (9 bp deletion). The small deletions resulted in frameshifts leading to the formation of premature stop codons. The 134C→A and 541C→T mutations caused the formation of stop codons likely to be responsible for drastic disruption of the HMBS structure (Ser45Ter, Gln181Ter). This is the first molecular study in AIP patients of Italian origin leading to the identification of four new mutations and three molecular defects that have already been described. Hum Mutat 15:480, 2000. © 2000 Wiley‐Liss, Inc.

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Acute intermittent porphyria: Characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G>T)

Cited by 11 publications

References 9 publications

Acute Intermittent Porphyria in Argentina: An Update

Acute Intermittent Porphyria in Argentina: An Update

Two new mutations (H106P and L178V) in the protoporphyrinogen oxidase gene in Argentinean patients with variegate porphyria

Molecular analysis of the hydroxymethylbilane synthase (HMBS) gene in Italian patients with acute intermittent porphyria: Report of four novel mutations

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