Medicine · 2023
A novel F8 variant in a Chinese hemophilia A family and involvement of X-chromosome inactivation: A case report.
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Zhang Honghong, Li Yinjie, Lv Xiaojuan, Mao Yuchan, Sun Yixi, Xu Ting
Аннотация
RATIONALE: Hemophilia A (HA) is an X-linked recessive bleeding disorder, which shows factor VIII (FVIII) deficiency caused by genetic variant in F8 gene.
PATIENT CONCERNS: Males 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.
DIAGNOSES: We 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.
INTERVENTIONS: We performed Androgen receptor gene (AR) assays and RT-PCR.
OUTCOMES: AR 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.
LESSONS: Our findings suggest that F8: c.6193T > G could be the cause of HA and that XCI affected the FVIII plasma levels in female carriers.
PATIENT CONCERNS: Males 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.
DIAGNOSES: We 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.
INTERVENTIONS: We performed Androgen receptor gene (AR) assays and RT-PCR.
OUTCOMES: AR 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.
LESSONS: Our findings suggest that F8: c.6193T > G could be the cause of HA and that XCI affected the FVIII plasma levels in female carriers.