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Case Reports
. 2024 Dec;71(12):e31332.
doi: 10.1002/pbc.31332. Epub 2024 Sep 17.

A de novo int22h-1/int22h-2-flanked Xq28 deletion-associated preferential X-inactivation in a female with severe hemophilia B

Wan-Chun Chen  1 , Hsiao-Jung Kao  2 , Pui-Yan Kwok  2   3 , Shyh-Shin Chiou  1   4   5 , Yu-Ling Kuo  6   7   8 , Wan-Yi Hsu  4 , Ping-Tao Lu  4 , Cian-Rong Wu  4 , Pei-Chin Lin  4   9
Affiliations
Case Reports

A de novo int22h-1/int22h-2-flanked Xq28 deletion-associated preferential X-inactivation in a female with severe hemophilia B

Wan-Chun Chen et al. Pediatr Blood Cancer. 2024 Dec.

Abstract

A 5-year-old female diagnosed with severe hemophilia B began experiencing frequent muscular and joint bleeds at 19 months old. Molecular studies, including Sanger sequencing, Giemsa banding, human androgen receptor (HUMARA) assay, array-based comparative genomic hybridization (aCGH), whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA), revealed a heterozygous factor IX (F9) intron 3 substitution (c.277+1G>T) inherited from her mother and a de novo heterozygous 441 kb deletion in the Xq28 region, which flanked intron 22 homologous regions 1 (int22h1) and 2 (int22h2). This rare genetic profile explains her severe phenotype and guides hereditary consultation for family planning.

Keywords: factor IX gene variant; female hemophilia; hemophilia; int22h‐1/int22h‐2‐flanked Xq28 deletion; preferential X chromosome inactivation.

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References

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