Abstract
Prenatal exome sequencing (ES) can establish rare genetic diagnoses in a fetus but may also lead to occult genetic diagnosis in a biological parent. We present a case of dual fetal and maternal diagnosis by prenatal ES, in a fetus with unexplained anemia and in a pregnant patient with sickle cell disease (SCD) and recurrent unexplained hypoxia. ES identified a novel, likely pathogenic gamma globin variant, HbF Mission Bay HBG2 (c.86T > A, p.Leu29Gln), in both the fetus and mother. Deleterious variants in HBG2 have been associated with cyanosis, hypoxia, methemoglobinemia, and hemolytic anemia that are typically confined to infancy. In the pregnant patient who herself had a separate diagnosis of SCD, the HBG2 variant manifested with hypoxia as an infant herself, recurrent hypoxia in adulthood, and methemoglobinemia during pregnancy due to persistence of HbF. This same variant manifested in the fetus as anemia requiring multiple in utero transfusions as well as neonatal methemoglobinemia after birth.
