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Comparative multiplex dosage analysis detects whole exon deletions at the phenylalanine hydroxylase locus
Author(s) -
Gable Mary,
Williams Margaret,
Stephenson Anne,
Okano Yoshiyuki,
Ring Susan,
Hurtubise Melanie,
Tyfield Linda
Publication year - 2003
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.10199
Subject(s) - biology , exon , genetics , phenylalanine hydroxylase , multiplex , locus (genetics) , microbiology and biotechnology , genomic dna , complementary dna , gene , gene dosage , gene duplication , allele , tandem exon duplication , phenylalanine , gene expression , amino acid
We have developed quantitative comparative multiplex dosage analysis to detect altered copy number of regions of the phenylalanine hydroxylase gene. Out of 41 alleles (4% of 1,010 PKU chromosomes) on which a mutation had not been characterized previously, this technique has highlighted two novel mutations: deletions of exon 5 and of exon 6 on a total of eight alleles. Restriction‐enzyme digestion of genomic DNA and hybridization to an amplified segment of the phenylalanine hydroxylase (PAH) cDNA probe PAH 247 established the size of the deletion in five individuals to be between 700 and 900 bases. We also report somatic mosaicism in the parent of an affected child previously shown to have a deletion spanning exons 5 and 6. Finally, we report a putative duplication of a region encompassing exon 6 in an affected individual. Hum Mutat 21:379–386, 2003. © 2003 Wiley‐Liss, Inc.