A Novel Large Deletion Including the Major Regulatory Element Compounded with SEA Deletion Causing Hydrops-Fetalis-Syndrome.

MCS-R regulatory elements are very important for the synthesis of α-globin. Deletion of the major α-globin regulatory elements compounded with deletion of α-globin genes can cause Hb Bart's (c4) hydrops fetalis, which is the severe form of α-thalassemia. In this report, a 19-year-old female at the 16th week of gestation came to our center due to abnormal fetal cardiothoracic ratio and thickened placental depth. The electrophoresis result of fetal umbilical cord blood revealed the level of Hb Bart's band to be 87.6%, which suggested the fetus was Hb Bart's hydrops fetalis. Next generation sequencing screen using targeted capture was used to detect the genotype of the fetus to be -SEA deletion, βA/βA. Multiplex ligation-dependent probe amplification (MLPA) is very useful to detect copy number variation (deletions/duplications), the result of which suggested the existence of -SEA deletion compounded with the novel large deletion of the major α-globin regulatory element (MCS-R2, R1, R3 and R4). Using the self-designed MLPA probe, the deletion should extend from the telomere downstream and the downstream breakpoint was between 143702 and 144291(GRch38/hg18). The novel deletion was also observed in the fetus' father and grandfather who had mild anemia. Of cases with the MCS deletion compounded with α⁰-thalassemia, this was the earliest time when the fetus presented fetal edema. Our study gave more evidence for genetic counseling for MCS deletion.