Novel HMBS founder mutation and significant intronic polymorphism in Spanish patients with acute intermittent porphyria.
Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis, caused by a partial deficiency of hydroxymethylbilane synthase (HMBS). Knowledge of the nature of the HMBS mutations causing AIP in Spanish families is very limited. Here we report a novel 669_698del of the HMBS gene in twenty-two individuals from five independent Spanish AIP families, settled in Murcia (southeastern region of Spain). All mutation carriers shared a common disease associated haplotype indicating an ancestral founder effect. Identification of the 669_698del founder mutation allowed rapid and simple molecular diagnosis of AIP in families from this region in Spain. In addition, 771 + 58C>T in intron 12 on the non-669_698del allele was identified in six AIP patients, which promoted homozygous AIP misdiagnosis.
Unidad de Genética Médica del Servicio de Pediatría, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain. encarna.guillen@carm.es
E
E
Guillén-Navarro
P
P
Carbonell
G
G
Glover
M
M
Sánchez-Solís
A
A
Fernández-Barreiro
D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D017118:Porphyria, Acute Intermittent / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
D011163:Hydroxymethylbilane Synthase