• Honghong Zhang, Yinjie Li, Xiaojuan Lv, Yuchan Mao, Yixi Sun, and Ting Xu.
• Department of Pediatrics, Hangzhou Children's Hospital, Hangzhou, Zhejiang, China.
• Medicine (Baltimore). 2023 May 5; 102 (18): e33665e33665.

RationaleHemophilia A (HA) is an X-linked recessive bleeding disorder, which shows factor VIII (FVIII) deficiency caused by genetic variant in F8 gene.Patient ConcernsMales with F8 variants are affected, whereas female carriers with a wide range of FVIII levels are usually asymptomatic, it is possible that different X-chromosome inactivation (XCI) may effect the FVIII activity.DiagnosesWe identified a novel variant F8: c.6193T > G in a Chinese HA proband, it was inherited from the mother and grandmother with different FVIII levels.InterventionsWe performed Androgen receptor gene (AR) assays and RT-PCR.OutcomesAR assays revealed that the X chromosome with the F8 variant was severely skewed inactivated in the grandmother with higher FVIII levels, but not in the mother with lower FVIII levels. Further, RT-PCR of mRNA confirmed that only the wild allele of F8 was expressed in the grandmother, with lower expression in the wild allele of the mother.LessonsOur findings suggest that F8: c.6193T > G could be the cause of HA and that XCI affected the FVIII plasma levels in female carriers.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

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