{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T13:38:28Z","timestamp":1765373908086,"version":"3.46.0"},"reference-count":43,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hemophilia A (HA) is an X-linked recessive bleeding disorder that predominantly affects males but rarely manifests clinically in females. We report an unusual case of a woman with HA carrying a de novo heterozygous F8 variant, skewed X chromosome inactivation (XCI), and mosaic monosomy X without the Turner syndrome phenotype. DNA was extracted from whole blood. After excluding F8 inversions and large rearrangements, Sanger sequencing of coding regions was performed. XCI was assessed by STR analysis of the AR gene. Haplotypes were identified by fragment analysis of three polymorphic sites. Karyotyping was performed using G-banding. A heterozygous missense variant in the F8 gene, c.6545G&gt;A (p.Arg2182His), was detected with allelic imbalance. STR analysis confirmed ~93% skewed XCI. Karyotyping revealed mosaicism: 45,X [7]\/46,XX [14]. Neither parent carried the c.6545G&gt;A variant or karyotype aberrations. We suggest that 46,XX cells carried c.6545G\/A with preferential inactivation of the normal X chromosome, whereas 45,X0 cells carried the mutant allele only. The limited proportion of active normal X chromosomes led to a mild rather than severe phenotype. This case highlights complex genetic mechanisms underlying HA in females and underscores the importance of comprehensive molecular and cytogenetic testing for accurate diagnosis, clinical management, and genetic counseling.<\/jats:p>","DOI":"10.3390\/ijms262411899","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:20:57Z","timestamp":1765369257000},"page":"11899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Rare Case of Mild Hemophilia A in a Female with Mosaic Monosomy X and a De Novo F8 Variant"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-8146","authenticated-orcid":false,"given":"Olesya","family":"Pshenichnikova","sequence":"first","affiliation":[{"name":"Laboratory of Genetic Engineering, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5669-3948","authenticated-orcid":false,"given":"Valentina","family":"Salomashkina","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Engineering, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8986-7572","authenticated-orcid":false,"given":"Olga","family":"Yastrubinetskaya","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Department of Hematology and Hemostasis Disorders, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4492","authenticated-orcid":false,"given":"Vadim","family":"Surin","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Engineering, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-4701","authenticated-orcid":false,"given":"Olesya","family":"Mishina","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetic Diagnostics, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5431-2240","authenticated-orcid":false,"given":"Galina","family":"Alimova","sequence":"additional","affiliation":[{"name":"Laboratory of Karyology, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-652X","authenticated-orcid":false,"given":"Tatiana","family":"Obukhova","sequence":"additional","affiliation":[{"name":"Laboratory of Karyology, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7074-0926","authenticated-orcid":false,"given":"Nadezhda","family":"Zozulya","sequence":"additional","affiliation":[{"name":"Clinical and Diagnostic Department of Hematology and Hemostasis Disorders, National Medical Research Center for Hematology, Novy Zykovski Lane 4a, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/312326a0","article-title":"Characterization of the Human Factor VIII Gene","volume":"312","author":"Gitschier","year":"1984","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.transci.2019.08.013","article-title":"Women and Inherited Bleeding Disorders\u2014A Review with a Focus on Key Challenges for 2019","volume":"58","author":"Winikoff","year":"2019","journal-title":"Transfus. 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