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A defective splice site at the phenylalanine hydroxylase gene in phenylketonuria and benign hyperphenylalaninemia among Palestinian Arabs
Author(s) -
Kleiman Sandra,
Bernstein Jeanna,
Schwartz Gerard,
Eisensmith Randy C.,
Woo Savio L. C.,
Shiloh Yosef
Publication year - 1992
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380010413
Subject(s) - hyperphenylalaninemia , phenylalanine hydroxylase , genetics , biology , haplotype , allele , compound heterozygosity , intron , point mutation , gene , mutation , locus (genetics) , phenylalanine , splice , splice site mutation , exon , alternative splicing , amino acid
Phenylketonuria (PKU) and benign hyperphenylalaninemia (HPA) result from different combinations of mutations at the locus for phenylalanine hydroxylase (PAH). While some of these mutations show widespread ethnic distribution, others are unique to specific communities. We report here the first point mutation common among Palestinian Arabs. The mutation (IVS2nt 1) involves a dinucleotide substitution (Gg→Aa) at the donor splice site of intron 2 of the PAH gene and abolishes a recognition site of the restriction enzyme Mnl I. IVS2nt 1 is associated with two PAH polymorphic haplotypes, 7 and 42. Homozygotes for this mutation are affected with severe, classical PKU. Compound heterozygotes carrying the IVS2nt 1 allele and one of several other yet unknown mutations show different degrees of benign HPA. © 1992 Wiley‐Liss, Inc.