Molecular exclusion of haemoglobin SD disease by prenatal diagnosis

The most common Hb D variant, Haemoglobin D (Hb D) Los Angeles is caused by a glutamic acid to glutamine substitution at codon 121 of the beta globin gene. Although asymptomatic in the heterozygous form, inheritance together with an Hb S allele can result in a severe disease similar to sickle-cell anaemia that is referred to as Hb SD disease. Prenatal diagnosis for Hb SD disease was requested by an at-risk couple of Irish/English descent. Prenatal diagnosis was performed on DNA isolated from chorionic villi at 12 weeks' gestation using dot blot and allele-specific oligonucleotide hybridization for the HbS mutation, and two independent approaches, restriction fragment analysis and ARMS (amplification refractory mutation system) for the detection of the Hb D Los Angeles mutation. The fetus was found to be heterozygous for the HbS mutation, but did not inherit the HbD mutation. Thus, a reliable and rapid prenatal diagnosis for the Hb SD disease can be achieved by molecular diagnosis.