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PAH-specific ACMG/AMP criteria applied: PVS1: Initiation codon variant; PM2: gnomAD MAF=0.00002; PP4_Moderate: Seen in PKU patients. BH4 disorders ruled out. (PMID:2574002); PS3: <3% (PMID:9450897). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PVS1, PM2, PP4_Moderate, PS3).
Met criteria codes
Seen in PKU patients. BH4 disorders ruled out.
Analysis of RFLP haplotypes and mutations revealed a novel mutation, an A-to-G transition (met----val) in codon 1 (the translation-initiation codon). It occurred on 5 of the 18 mutant chromosomes. A proband homozygous for this mutation had the PKU phenotype. The appropriate biochemical tests were done to rule out disorders of tetrahydrobiopterin homeostasis.
Initiation codon variant
< 3 PAH enzyme activity as % of wild type. (p91023(B)/COS
Approved on: 2018-08-07
Published on: 2018-12-10
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