Clinical biochemistry · 2012
The spectrum of mutations identified in Cypriot patients with phenylalanine hydroxylase deficiency detected through neonatal screening.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Georgiou Theodoros, Ho Gladys, Vogazianos Marios, Dionysiou Maria, Nicolaou Alexia, Chappa Georgia, Nicolaides Paola, Stylianidou Goula, Christodoulou John, Drousiotou Anthi
Аннотация
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 (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.
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 (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.