Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations

被引:31
作者
Daniele, A.
Cardillo, G.
Pennino, C.
Carbone, M. T.
Scognamiglio, D.
Correra, A.
Pignero, A.
Castaldo, G.
Salvatore, F.
机构
[1] CEINGE Biotecnol Avanzate, Scarl, I-80145 Naples, Italy
[2] Univ Naples Federico 2, Dipartimento Biochim & Biotecnol Med, Naples, Italy
[3] Univ Molise, Dipartimento Sci Salute, Campobasso, Italy
[4] Osped SS Annunziata ASL Na1, Ctr Screening Fenilchetonuria, Naples, Italy
[5] Univ Molise, Fac Sci, Isernia, Italy
[6] SEMM, Sect Naples, Naples, Italy
关键词
hyperphenylalaninemia (HPA); phenylalanine hydroxylase (PAH); mutation detection; Southern Italy;
D O I
10.1111/j.1469-1809.2006.00328.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:185 / U1
页数:10
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