Prenatal Diagnosis of the WAS R86H Sequence Variation in Heterozygous Twins

Extract

To the Editor:

A healthy 28-year-old woman was heterozygous for the Wiskott–Aldrich syndrome gene (WAS) sequence variation, and the syndrome-causing variant was inherited by her first-born son (Fig. 1¹ ). The 2.5-year-old hemizygous boy developed characteristic features of the WAS, including eczema, thrombocytopenia, and recurrent infections of the lower respiratory tract from early infancy. The mother presented recently with a new pregnancy, and the abdominal ultrasound scan obtained at 7 weeks of gestation revealed that she had conceived twins. We counseled the mother on the complexity and risks of invasive prenatal diagnostic procedures and made it clear that the potential risk of disease in a male fetus is 50%; nevertheless, she decided to continue her pregnancy and to undergo invasive prenatal evaluation. At 11 weeks of gestation, chorionic villus sampling by a transabdominal approach was performed with no complications. Rapid karyotyping revealed a male and a female fetus. We then isolated genomic DNA from the chorionic villus samples and performed bidirectional DNA sequencing of the WAS gene. Neither of the fetuses carried the R86H WAS sequence variant found in the mother and her son (Fig. 1¹ ).