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

Annals of Human Genetics

Volumn 71, Issue 2, 2007, Pages 185-193

  Daniele, A ^a,b,c   Cardillo, G ^a   Pennino, C ^a   Carbone, M T ^d   Scognamiglio, D ^d   Correra, A ^d   Pignero, A ^d   Castaldo, G ^a,b,c,e   Salvatore, Francesco ^a,b,e  

^a CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c UNIVERSITY OF MOLISE   (Italy)

^d Ospedale SS Annunziata   (Italy)

^e SEMM   (Italy)

Author keywords

Hyperphenylalaninemia (HPA); Mutation detection; Phenylalanine hydroxylase (PAH); Southern Italy

Indexed keywords

PHENYLALANINE 4 MONOOXYGENASE; TETRAHYDROBIOPTERIN;

ARTICLE; CHROMOSOME VARIANT; GENE AMPLIFICATION; GENE MUTATION; GENE SEQUENCE; GENOTYPE; HUMAN; HYPERPHENYLALANINEMIA; INFANT; ITALY; MAJOR CLINICAL STUDY; MUTATION RATE; MUTATIONAL ANALYSIS; NEWBORN SCREENING; PHENOTYPE; PHENYLKETONURIA; PRIORITY JOURNAL; ALLELE; EPIDEMIOLOGY; EXON; FEMALE; GENETICS; INTRON; MALE; MUTATION; NEWBORN; NUCLEOTIDE SEQUENCE; PROMOTER REGION;

ALLELES; DNA MUTATIONAL ANALYSIS; EPIDEMIOLOGY, MOLECULAR; EXONS; FEMALE; GENOTYPE; HUMANS; INFANT, NEWBORN; INTRONS; ITALY; MALE; MUTATION; NEONATAL SCREENING; PHENOTYPE; PHENYLALANINE HYDROXYLASE; PHENYLKETONURIAS; PROMOTER REGIONS (GENETICS);

EID: 34047276096     PISSN: 00034800     EISSN: 14691809     Source Type: Journal    
DOI: 10.1111/j.1469-1809.2006.00328.x     Document Type: Article

References (30)

1. Bardelli, T., Donati, M. A., Gasperini, S., Ciani, F., Belli, F., Blau, N., Morrone, A. & Zammarchi, E. (2002) Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia. Mol Genet Metab 77, 260-266.
2. Blau, N. & Erlandsen, H. (2004a) The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Mol Genet Metab 82, 101-111.
3. Blau, N. & Scriver, C. R. (2004b) New approaches to treat PKU: How far are we? Mol Genet Metab 81, 1-2.
4. Blau, N., Thöny, B., Cotton, R. G. H. & Hyland, K. (2001), Disorders of tetrahydrobiopterin and related biogenic amines. In: The metabolic and molecular basis of inherited disease (eds. C.R. Scriver, A.L. Beaudet, W.S. Sly & D. Valle), pp. 1725-1776. Basel: McGraw Hill.
5. Bosco, P., Ceratto, N., Cali, F., Goltsov, A. A., Eisensmith, R. C., Novelli, G., Dalla Piccola, B. & Romano, V. (1996) RFLP discordance in a PKU family due to a deletion in the PAH gene. Turk J Pediatr 38, 497-504.
6. Castaldo, G., Polizzi, A., Tomaiuolo, R., Cazeneuve, C., Girodon, E., Santostasi, T., Salvatore, D., Raia, V., Rigillo, N., Goossens, M. & Salvatore, F. (2005) Comprehensive cystic fibrosis mutation epidemiology and haplotype characterization in a southern Italian population. Ann Hum Genet 69, 15-24.
7. Chien, Y. H., Chiang, S. C., Huang, A., Chou, S. P., Tseng, S. S., Huang, Y. T. & Hwu, W. L. (2004) Mutation spectrum in Taiwanese patients with phenylalanine hydroxylase deficiency and a founder effect for the R241C mutation. Hum Mutat 23, 206.
8. Desviat, L. R., Perez, B., Belanger-Quintana, A., Castro, M., Aguado, C., Sanchez, A., Garcia, M. J., Martinez-Prado, M. & Ugarte, M. (2004) Tetrahydrobiopterin responsiveness: Results of BH4 loading test in 31 Spanish PKU patients and correlation with their genotype. Mol Genet Metab 83, 157-162.
9. Dipple, K. M. & McCabe, E. R. B. (2000) Modifier genes convert "simple" mendelian disorders to complex traits. Mol Genet Metab 71, 43-50.
10. Erlandsen, H., Patch, M. G., Gamez, A., Straub, M. & Stevens, R. C. (2003) Structural studies on phenylalanine hydroxylase and implications toward understanding and treating phenylketonuria. Pediatrics 112, 1557-1565.
11. 4 responsiveness in patients with mild forms of hyperphenylalaninemia and phenylketonuria. J Inherit Metab Dis 24, 213-230.
12. Giannattasio, S., Dianzani, I., Lattanzio, P., Spada, M., Romano, V., Cali, F., Andria, G., Ponzone, A., Marra, E. & Piazza, A. (2001) Genetic heterogeneity in five Italian regions: Analysis of PAH mutations and minihaplotypes. Hum Hered 52, 154-159.
13. Goltsov, A. A., Eisensmith, R. C., Konecki, D. S., Lichter-Konecki, U. & Woo, S. L. C. (1992) Association between mutations and a VNTR in the human phenylalanine hydroxylase gene. Am J Hum Genet 51, 627-636.
14. Goltsov, A. A., Eisensmith, R. C., Naughton, E. R., Jin, L., Chakraborty, R. & Woo, S. L. C. (1993) A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria. Hum Mol Genet 2, 577-581.
15. Guldberg, P., Rey, F., Zschocke, J., Romano, V., Francois, B., Michiels, L., Ullrich, K., Hoffmann, G. F., Burgard, P., Schmidt, H., Meli, C., Riva, E., Dianzani, I., Ponzone, A., Rey, J. & Guttler, F. (1998) A European multicenter study of phenylalanine hydroxylase deficiency: Classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am J Hum Genet 63, 71-79.
16. Guthrie, R. & Susi, A. (1963) A simple phenylalanine method for detecting Phenylketonuria in large populations of newborn infants. Pediatrics 32, 338-343.
17. Kleiman, S., Vanagaite, L., Bernstein, J., Schwartz, G., Brand, N., Elitzur, A., Woo, S. L. & Shiloh, Y. (1993) Phenylketonuria: variable phenotypic outcomes of the R261Q mutation and maternal PKU in the offspring of a healthy homozygote. J Med Genet 30, 284-288.
18. Pagani, F., Stuani, C., Tzetis, M., Kanavakis, E., Efthymiadou, A., Doudounakis, S., Casals, T. & Baralle, F. E. (2003) New type of disease causing mutations: The example of the composite exonic regulatory elements of splicing in CFTR exon 12. Hum Mol Genet 12, 1111-1120.
19. Rendine, S., Calafell, F., Cappello, N., Gagliardini, R., Caramia, G., Rigillo, N., Silvetti, M., Zanda, M., Miano, A., Battistini, F., Marianelli, L., Taccetti, G., Diana, M. C., Romano, L., Romano, C., Giunta, A., Padoan, R., Pianaroli, A., Raia, V., De Ritis, G., Battistini, A., Grzincich, G., Japichino, L., Pardo, F., Piazza, A. et al. (1997) Genetic history of cystic fibrosis mutations in Italy. I. Regional distribution. Ann Hum Genet 61, 411-424.
20. Rivera, I., Cabral, A., Almeida, M., Leandro, P., Carmona, C., Eusebio, F., Tasso, T., Vilarinho, L., Martins, E., Lechner, M. C., Tavares de Almeida, I., Konecki, D. S. & Lichter-Konecki, U. (2000) The correlation of genotype and phenotype in Portuguese hyperphenylalaninemic patients. Mol Genet Metab 69, 195-203.
21. Romano, V., Lio, D., Cali, F., Scola, L., Leggio, L., D'Anna, C., De Leo, G. & Salermo, A. (2001) A methodological strategy for PAH genotyping in populations with a marked molecular heterogeneity of hyperphenylalaninemia. Mol Cell Probes 15, 13-19.
22. Salvatore, F., Scudiero, O., Castaldo, G. (2002) Genotype-phenotype correlation in cystic fibrosis: The role of modifier genes. Am J Med Genet 111, 88-95.
23. Scriver, C. R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Waters, P. J., Ryan, S., McDonald, D. & Sarkissian, C. (2003) PAHdb 2003: What a locus-specific knowledgebase can do? Hum Mutat 21, 333-344.
24. Scriver, C. R., Kaufman, S., Eisensmith, R. C. & Woo, S. L. C. (2001), The hyperphenylalaninemias. In: The metabolic and molecular basis of inherited disease (eds. C.R. Scriver, A.L. Beaudet, W.S. Sly & D. Valle), pp. 1667-1724. Basel: McGraw Hill.
25. Scriver, C. R. & Waters, P. J. (1999) Monogenic traits are not simple: Lessons from phenylketonuria. Trends Genet 15, 267-272.
26. Spaapen, L. J. M. & Rubio-Gozalbo, M. E. (2003) Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency, state of the art. Mol Genet Metab 78, 93-99.
27. Taruscio, D., Falbo, V., Floridia, G., Salvatore, M., Pescucci, C., Cantafora, A., Marongiu, C., Baroncini, A., Calzolari, E., Cao, A., Castaldo, G., Bricarelli, F. D., Guanti, G., Nitsch, L., Pignatti, P. F., Rosatelli, C., Salvatore, F. & Zuffardi, O. (2004) Quality assessment in cytogenetic and molecular genetic testing: The experience of the Italian Project on Standardization and Quality Assurance. Clin Chem Lab Med 42, 915-921.
28. Waters, P. J. (2003) How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: Insights from in vitro expression. Hum Mutat 21, 357-369.
29. Zschocke, J. (2003) Phenylketonuria mutations in Europe. Hum Mutat 21, 345-356.
30. Zschocke, J. & Hoffmann, G. F. (1999) Phenylketonuria mutations in Germany. Hum Genet 104, 390-398.