Identification of USP9X as a leukemia susceptibility gene.

TitleIdentification of USP9X as a leukemia susceptibility gene.
Publication TypeJournal Article
Year of Publication2023
AuthorsSisoudiya, SDushyant, Mishra, P, Li, H, Schraw, JM, Scheurer, ME, Salvi, S, Doddapaneni, H, Muzny, DM, Mitchell, D, Taylor, O, Sabo, A, Lupo, PJ, Plon, SE
JournalBlood Adv
Date Published2023 Aug 22
KeywordsFemale, Humans, Intellectual Disability, Leukemia, Loss of Function Mutation, Male, Mutation, Missense, Phenotype, Ubiquitin Thiolesterase

We recently reported that children with multiple birth defects have a significantly higher risk of childhood cancer. We performed whole-genome sequencing on a cohort of probands from this study with birth defects and cancer and their parents. Structural variant analysis identified a novel 5 kb de novo heterozygous inframe deletion overlapping the catalytic domain of USP9X in a female proband with multiple birth defects, developmental delay, and B-cell acute lymphoblastic leukemia (B-ALL). Her phenotype was consistent with female-restricted X-linked syndromic intellectual developmental disorder-99 (MRXS99F). Genotype-phenotype analysis including previously reported female probands (n = 42) demonstrated that MRXS99F probands with B-ALL (n = 3) clustered with subjects with loss-of-function (LoF) USP9X variants and multiple anomalies. The cumulative incidence of B-ALL among these female probands (7.1%) was significantly higher than an age- and sex-matched cohort (0.003%) from the Surveillance, Epidemiology, and End Results database (P 

Alternate JournalBlood Adv
PubMed ID37289514
PubMed Central IDPMC10425687
Grant ListR03 CA272955 / CA / NCI NIH HHS / United States

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