TY - JOUR
T1 - The spectrum of mutations identified in Cypriot patients with phenylalanine hydroxylase deficiency detected through neonatal screening
AU - Georgiou, Theodoros
AU - Ho, Gladys
AU - Vogazianos, Marios
AU - Dionysiou, Maria
AU - Nicolaou, Alexia
AU - Chappa, Georgia
AU - Nicolaides, Paola
AU - Stylianidou, Goula
AU - Christodoulou, John
AU - Drousiotou, Anthi
PY - 2012/5
Y1 - 2012/5
N2 - Objectives: The purpose of this study was to identify the mutations responsible for phenylalanine hydroxylase deficiency in Cypriot patients detected through neonatal screening. Design and 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 (BH 4) 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.
AB - Objectives: The purpose of this study was to identify the mutations responsible for phenylalanine hydroxylase deficiency in Cypriot patients detected through neonatal screening. Design and 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 (BH 4) 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.
KW - Cyprus
KW - Mutation analysis
KW - Neonatal screening
KW - PAH
KW - Phenylalanine hydroxylase
KW - Phenylketonuria
UR - http://www.scopus.com/inward/record.url?scp=84860209048&partnerID=8YFLogxK
U2 - 10.1016/j.clinbiochem.2012.01.026
DO - 10.1016/j.clinbiochem.2012.01.026
M3 - Article
C2 - 22330942
AN - SCOPUS:84860209048
SN - 0009-9120
VL - 45
SP - 588
EP - 592
JO - Clinical Biochemistry
JF - Clinical Biochemistry
IS - 7-8
ER -