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

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.