Spectrum of mutations in Lebanese patients with phenylalanine hydroxylase deficiency

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• 作者：Pascale E. Karam^a ; Rasha Shahabeddeen Alhamra^b ; Georges Nemer^b ; Julnar Usta^b ; ^{Justa@aub.edu.lb}
• 关键词：AV ; Arbitrary Value ; BH4 ; Tetrahydrobiopterin ; HR ; Homozygosity rate ; IVS ; Intervening sequences ; MHP ; Mild Hyperphenylalaninemia ; PAH ; Phenylalanine hydroxylase ; Phe ; Phenylalanine ; PKU ; phenylketonuria ; PRA ; Predicted residual activity
• 刊名：Gene
• 出版年：2013
• 出版时间：15 February, 2013
• 年：2013
• 卷：515
• 期：1
• 页码：117-122
• 全文大小：203 K

文摘

Phenylketonuria is an autosomal recessive inborn error of metabolism resulting from phenylalanine hydroxylase deficiency. Genetic basis of phenylalanine hydroxylase deficiency has been reported in various European and Asian countries with few reports available in Arab populations of the Mediterranean region. This is the first pilot study describing phenotype and genotype of 23 Lebanese patients with phenylketonuria. 48 % of the patients presented mainly with neurological signs at a mean age of 2 years 9 months, as newborn screening is not yet a nationwide policy. 56.5 % of the patients had classical phenylketonuria. Thirteen different mutations were identified: splice site 52 % , frameshift 31 % , and missense 17 % with no nonsense mutations. IVS10-11G>A was found mainly in Christians at high relative frequency whereas Muslims carried the G352fs and R261Q mutations. A rare splice mutation IVS7+1G>T, not described before, was identified in the homozygous state in one family with moderate phenylketonuria phenotype. Genotype-phenotype correlation using Guldberg arbitrary value method showed high consistency between predicted and observed phenotypes. Calculated homozygosity rate was 0.07 indicating the genetic heterogeneity in our patients. Our findings underline the admixture of different ethnicities and religions in Lebanon that might help tracing back the PAH gene flux history across the Mediterranean region.