title: Large heterozygous deletion masquerading as homozygous missense mutation: a pitfall in diagnostic mutation analysis.
abstract: The clinical use of molecular analyses in recessive disorders relies on the exact characterization of both mutant alleles in the affected patient. This can be problematic when only part of the gene is examined or when relevant DNA alterations are not recognized by standard methods. We present a child in whom phenylketonuria was apparently caused by homozygosity for the mutation E390G in exon 11 of the phenylalanine hydroxylase (PAH) gene. However, the clinical severity of the disease was not quite as mild as expected, the mutation was not identified in the father despite confirmed paternity, and the paternal allele showed a highly unusual pattern of polymorphic markers in the PAH gene. Presence of a large deletion involving exons 9, 10 and 11 of the phenylalanine hydroxylase gene was confirmed by long-range PCR. Diagnostic DNA analyses should include a comprehensive examination of the whole relevant gene in the patient and confirmation of carrier status in both parents.
authors.affiliation: Department of Paediatrics, Philipps University, Marburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Zschocke
authors.forename: E
authors.initials: E
authors.lastname: Quak
authors.forename: A
authors.initials: A
authors.lastname: Knauer
authors.forename: B
authors.initials: B
authors.lastname: Fritz
authors.forename: M
authors.initials: M
authors.lastname: Aslan
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons; D017353:Gene Deletion; D006580:Genetic Carrier Screening; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D020125:Mutation, Missense; D015997:Neonatal Screening; D010334:Paternity; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D010651:Phenylalanine Hydroxylase