title: The spectrum of mutations identified in Cypriot patients with phenylalanine hydroxylase deficiency detected through neonatal screening.
abstract: OBJECTIVE
  The purpose of this study was to identify the mutations responsible for phenylalanine hydroxylase deficiency in Cypriot patients detected through neonatal screening.
  
  
  METHODS
  Analysis of the PAH gene was performed by direct sequencing of the patients' genomic DNA, MLPA analysis and real-time PCR.
  
  
  RESULTS
  Among 22 independent alleles thirteen previously described mutations were detected (detection rate 100%), all in compound heterozygosity: p.Arg395Gly (18.2%), c.168+5G>C (13.6%), p.EX3del (9%), c.1066-11G>A (9%), p.Ala403Val (9%), p.Glu178Gly (9%), p.Ser70Pro (4.5%), p.Arg241His (4.5%), p.Phe55fs (4.5%), p.Arg158Gln (4.5%), p.Asp222Gly (4.5%), p.Ala300Ser (4.5%), p.Pro225Thr (4.5%). Of the ten different genotypes, three have been previously reported to be associated with a mild clinical phenotype and to respond to tetrahydrobiopterin (BH₄) administration.
  
  
  CONCLUSIONS
  Marked genetic heterogeneity was found in Cypriot patients with hyperphenylalaninemia with two mutations accounting for 32% of the alleles. Most of the mutations detected have been found in other European and Mediterranean populations.
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Georgiou
authors.forename: Gladys
authors.initials: G
authors.lastname: Ho
authors.forename: Marios
authors.initials: M
authors.lastname: Vogazianos
authors.forename: Maria
authors.initials: M
authors.lastname: Dionysiou
authors.forename: Alexia
authors.initials: A
authors.lastname: Nicolaou
authors.forename: Georgia
authors.initials: G
authors.lastname: Chappa
authors.forename: Paola
authors.initials: P
authors.lastname: Nicolaides
authors.forename: Goula
authors.initials: G
authors.lastname: Stylianidou
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.forename: Anthi
authors.initials: A
authors.lastname: Drousiotou
mesh_terms: D000483:Alleles; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives; D003535:Cyprus / Q000453:epidemiology; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D059645:Mutation Rate; D020125:Mutation, Missense; D015997:Neonatal Screening / Q000379:methods*; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D001708:Biopterins; D010651:Phenylalanine Hydroxylase; C003402:sapropterin