Identification of Mutations in the Bruton's Tyrosine Kinase Gene, Including a Novel Genomic Rearrangements Resulting in Large Deletion, in Korean X-linked Agammaglobulinemia Patients
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Mutations in the Bruton's tyrosine kinase ( BTK) gene are responsible for X-linked agammaglobulinemia (XLA). We identified BTK mutations in six patients with presumed XLA from unrelated Korean families. Four out of six mutations were novel: two missense mutations (P565T, C154Y), a point mutation in a splicing donor site (IVS11+1G>A), and a large deletion (a 6.1-kb deletion including BTK exons 11-18). The large deletion, identified by long-distance PCR, revealed Alu-Alu mediated recombination extended from an Alu sequence in intron 10 to another Alu sequence in intron 18, spanning a distance of 6.1 kb. The two known mutations consisted of one missense (G462D) mutation, and a point mutation in a splicing acceptor site (IVS7-9A>G). This study suggests that large genomic rearrangements involving Alu repeats are few but an important component of the spectrum of BTK mutations.
van de Kooij B, Kruswick A, van Attikum H, Yaffe M Nat Commun. 2022; 13(1):5295.
PMID: 36075911 PMC: 9458747. DOI: 10.1038/s41467-022-32743-w.
Jain A, Madathil Govindaraj G, Edavazhippurath A, Faisal N, Bhoyar R, Gupta V PLoS One. 2021; 16(7):e0254407.
PMID: 34252140 PMC: 8274882. DOI: 10.1371/journal.pone.0254407.
Yeh Y, Hsieh M, Lee W, Huang J, Chen L, Yeh K Front Immunol. 2020; 11:2001.
PMID: 33013854 PMC: 7498534. DOI: 10.3389/fimmu.2020.02001.
The contribution of alu elements to mutagenic DNA double-strand break repair.
Morales M, White T, Streva V, DeFreece C, Hedges D, Deininger P PLoS Genet. 2015; 11(3):e1005016.
PMID: 25761216 PMC: 4356517. DOI: 10.1371/journal.pgen.1005016.
Aygun N Sci Rep. 2015; 5:8300.
PMID: 25657065 PMC: 4319165. DOI: 10.1038/srep08300.