title: Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection.
abstract: BACKGROUND
  First, to establish the mutations of the protoporphyrinogen-oxidase (PPOX) gene in four Spanish patients with variegate porphyria (VP). Second, study of carrier status detection in the families, including a four-generation Balearic family. Third, evaluation of the results of carrier detection screening methods.
  
  
  METHODS
  Blood samples of four patients and of 139 members belonging to four families, including four generations of a Balearic family were processed for mutation analysis of the 13 exons of PPOX gene. Biochemical studies were performed together (blood and faecal porphyrin analysis) and plasma fluorescence scanning for 626 nm peak emission detection. A questionnaire regarding clinical manifestations was submitted to all family members studied.
  
  
  RESULTS
  Single strand conformational analysis (SSCP) of DNA allowed the detection of the following mutations: W224R, 746delT: exon 7, 1077-1082insC: exon 10, and IVS6+2T-->A. Mutation was present in 19 of the 139 members of the families studied. Clinical manifestations or biochemical alterations were checked in the carriers detected and found as not relevant or not present. Only 11 members of the 19 mutation-bearing individuals showed plasma fluorescence PV peak positivity.
  
  
  CONCLUSIONS
  Demonstration of gene mutation is the most reliable means of detecting carriers in studies of variegate porphyria families. DNA analysis is the most sensitive carrier detection method and also allows transmission behaviour of the genetic defect to be established in successive generations of the affected families.
authors.affiliation: Department of Dermatology, Facultat de Medicina, Universitat de Barcelona, Spain. 4908mlc@comb.cat
authors.forename: M
authors.initials: M
authors.lastname: Lecha
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: S
authors.initials: S
authors.lastname: Puig
authors.forename: J
authors.initials: J
authors.lastname: Orfila
authors.forename: M
authors.initials: M
authors.lastname: Milà
authors.forename: J
authors.initials: J
authors.lastname: To-Figueras
authors.forename: C
authors.initials: C
authors.lastname: Muñoz
authors.forename: P
authors.initials: P
authors.lastname: Mercader
authors.forename: C
authors.initials: C
authors.lastname: Herrero
mesh_terms: D000328:Adult; D005091:Exons; D005190:Family; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D046350:Porphyria, Variegate / Q000235:genetics*; D050768:Protoporphyrinogen Oxidase / Q000235:genetics*; D013030:Spain; D011795:Surveys and Questionnaires
chemical_list: D050768:Protoporphyrinogen Oxidase