Abstract:

We report a case of a child with haemophilia A complicated by compound heterozygous variants in the CYP21A2 gene. Routine tests upon the child′s admission indicated the abnormal coagulation function. Whole exome sequencing (WES) analysis revealed that the child had the compound heterozygous variants c.292 + 1G>A and c.-113G>A in the CYP21A2 gene. Verified by Sanger sequencing, the c.-113G>A site variant was inherited from the mother, and this site was rated as a likely pathogenic variant. The c.292 + 1G>A site variant was inherited from the father, and this site was rated as a pathogenic variant. Since WES did not detect the variants highly correlated with the child′s current clinical phenotype, and the clinical phenotype highly suggested haemophilia, long-range polymerase chain reaction (LR-PCR) was simultaneously carried out. The results of LR-PCR indicated an inversion of intron 22 in F8 gene. The child′s mother was a carrier, while the father had a normal genetic profile. After admission, the child received symptomatic treatment and supplementation with exogenous factor Ⅷ, and then was discharged in an improved condition. During the follow-up, the child has been regularly receiving exogenous supplementation of factor Ⅷ, and the condition remains stable with no other abnormalities. The genetic diagnosis of the child was clarified through the combined use of WES and LR-PCR, which provided us a basis for genetic counseling of family members, future prenatal diagnosis and the subsequent management.

Key words: Hemophilia A, Adrenal hyperplasia, congenital, Whole exome sequencing, Polymerase chain reaction, F8 gene, CYP21A2 gene