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Large heterozygous deletion masquerading as homozygous missense mutation: A pitfall in diagnostic mutation analysis
Author(s) -
Zschocke J.,
Quak E.,
Knauer A.,
Fritz B.,
Aslan M.,
Hoffmann G. F.
Publication year - 1999
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005527731397
Subject(s) - missense mutation , genetics , exon , phenylalanine hydroxylase , mutation , allele , biology , gene , compound heterozygosity , human genetics , mutation testing , gene mutation , allelic heterogeneity , mutant , phenylalanine , amino acid
Abstract The clinical use of molecular analyses in recessive disorders relies onthe exact characterization of both mutant alleles in the affected patient. Thiscan 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.