Hyperphenylalaninemia (HPA) comprises a group of autosomal recessive disorders mainly caused by phenylalanine hydroxylase (PAH) gene mutations. We investigated PAH mutations in 126 HPA patients from Southern Italy who were identified in a neonatal screening program. The promoter, coding and exon-flanking intronic sequences of the PAH gene were amplified and sequenced. Mutations were identified in 240/249 alleles (detection rate: 96.4%). We found 60 gene variants; the most frequent were p.R261Q (15.7% of alleles), p.A403V (11.6% of alleles) and c.1066-11G > A (8.8% of alleles). The remaining mutations were rare, and ten are novel. This mutation epidemiology differs from that reported for Northern Italy and other European countries. We also identified several discordant genotype/phenotype correlations. About two-thirds of all mild phenylketonuria patients showed at least one tetrahydrobiopterin (BH4)-responsive mutation, and are thus candidates for a customized therapeutic approach.
Molecular epidemiology of phenylalanine hydroxilase deficiency in Southern Italy: a 96% detection rate with ten novel mutations / Daniele, A; Cardillo, Giuseppe; Pennino, C; Carbone, Mt; Scognamiglio, D; Correra, A; Pignero, A; Castaldo, Giuseppe; Salvatore, Francesco. - In: ANNALS OF HUMAN GENETICS. - ISSN 0003-4800. - ELETTRONICO. - 71:2(2007), pp. 185-193. [10.1111/j.1469-1809.2006.00328.x]
Molecular epidemiology of phenylalanine hydroxilase deficiency in Southern Italy: a 96% detection rate with ten novel mutations.
DANIELE A;CASTALDO, GIUSEPPE;SALVATORE, FRANCESCO
2007
Abstract
Hyperphenylalaninemia (HPA) comprises a group of autosomal recessive disorders mainly caused by phenylalanine hydroxylase (PAH) gene mutations. We investigated PAH mutations in 126 HPA patients from Southern Italy who were identified in a neonatal screening program. The promoter, coding and exon-flanking intronic sequences of the PAH gene were amplified and sequenced. Mutations were identified in 240/249 alleles (detection rate: 96.4%). We found 60 gene variants; the most frequent were p.R261Q (15.7% of alleles), p.A403V (11.6% of alleles) and c.1066-11G > A (8.8% of alleles). The remaining mutations were rare, and ten are novel. This mutation epidemiology differs from that reported for Northern Italy and other European countries. We also identified several discordant genotype/phenotype correlations. About two-thirds of all mild phenylketonuria patients showed at least one tetrahydrobiopterin (BH4)-responsive mutation, and are thus candidates for a customized therapeutic approach.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.