False non-paternity in a family for prenatal diagnosis of β-thalassaemia

Abstract

Initial screening for the common β-thalassaemia mutations with allele-specific oligonucleotide probe in an at-risk family suggested non-paternity. Subsequent DNA fingerprinting of the members proved otherwise. The mother had a codon 41/42 frameshift mutation and the father's defect, determined by direct sequencing of PCR-amplified β gene, was a codon 43 nonosense mutation. In the affected children, the close proximity of these two defects resulted in the absence of a hybridization signal to the normal probe in that region and a wrong assumption of homozygosity for the codon 41/42 mutation. The non-reactivity of the father's amplified DNA to the codon 41/42 thalassaemic probe accounted for the initial wrong conclusion of non-paternity. Since prior screening for β-thalassaemia mutations is done in all prenatal diagnosis programmes and concomitant inheritance of these two defects is relatively common in the Chinese, this 'artefact' of false non-paternity is worth noting.