Molecular Analysis of 55 Spanish Patients with Acute Intermittent Porphyria
| Autor: | Rafael Enríquez-de-Salamanca, María-José Borrero-Corte, Manuel Méndez, María-José Morán-Jiménez, Silvia Díaz-Díaz, Inmaculada García-Pastor, Francisco-Javier Castelbón-Fernandez, Fátima Jara-Rubio |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male prokaryotic expression lcsh:QH426-470 Adolescent Genotype Hydroxymethylbilane Synthase Porphobilinogen deaminase RNA Splicing DNA Mutational Analysis Gene mutation Polymerase Chain Reaction Article porphyria 03 medical and health sciences Young Adult 0302 clinical medicine Genetics medicine Missense mutation Humans acute intermittent porphyria Genetics (clinical) mutation analysis Acute intermittent porphyria Splice site mutation business.industry splicing defect Middle Aged medicine.disease Penetrance hydroxymethylbilane synthase lcsh:Genetics 030104 developmental biology Porphyria Spain Porphyria Acute Intermittent Mutation Female Disease Susceptibility business 030217 neurology & neurosurgery Biomarkers porphobilinogen deaminase |
| Zdroj: | Genes Volume 11 Issue 8 Genes, Vol 11, Iss 924, p 924 (2020) |
| ISSN: | 2073-4425 |
| Popis: | Acute intermittent porphyria (AIP) results from a decreased activity of hepatic hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway. AIP is an autosomal dominant disorder with incomplete penetrance, characterized by acute neurovisceral attacks precipitated by several factors that induce the hepatic 5-aminolevulinic acid synthase, the first enzyme in the heme biosynthesis. Thus, a deficiency in HMBS activity results in an overproduction of porphyrin precursors and the clinical manifestation of the disease. Early diagnosis and counselling are essential to prevent attacks, and mutation analysis is the most accurate method to identify asymptomatic carriers in AIP families. In the present study, we have investigated the molecular defects in 55 unrelated Spanish patients with AIP, identifying 32 HMBS gene mutations, of which six were novel and ten were found in more than one patient. The novel mutations included a missense, an insertion, two deletions, and two splice site variants. Prokaryotic expression studies demonstrated the detrimental effect for the missense mutation, whereas reverse transcription-PCR and sequencing showed aberrant splicing caused by each splice site mutation. These results will allow for an accurate diagnosis of carriers of the disease in these families. Furthermore, they increase the knowledge about the molecular heterogeneity of AIP in Spain. |
| Databáze: | OpenAIRE |
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