Hemophilia B is an X-linked bleeding disorder caused by deficient coagulation factor IX from a mutation in the F9 gene. Here, we report a family with two brothers having severe hemophilia B inherited from a mother with low-level somatic mosaicism of a F9 mutation. The
proband was a 2-year-old boy with severe hemophilia B from a hemizygous mutation of F9, c.464G>A (p.Cys155Tyr). He was the first child and was considered a sporadic case based on the lack of family history of bleeding diathesis. His mother was tested for carrier status and was determined
to be homozygous for wild-type genotypes (noncarrier). Subsequently, however, his brother was born and also had severe hemophilia B from Cys155Tyr. This prompted us to review the chromatogram of the mother, which revealed a small peak corresponding to the mutant genotype. On suspicion of somatic
low-level mosaicism in the mother, we further performed allele-specific PCR and thymine and adenine cloning, and confirmed the presence of the mutant allele in the mother. To our knowledge, this is the first case of maternal somatic mosaicism for a cytosine-phosphate-guanine transition mutation
in hemophilia B. The acknowledgment of somatic mosaicism and further molecular investigation are important in sporadic hemophilia B to deliver informative genetic counseling and risk assessment.
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Document Type: Research Article
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine
Samsung Biomedical Research Institute, Samsung Medical Center
Korea Hemophilia Foundation
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Cardiac & Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
December 1, 2015