title: Genetic analysis of contiguous X-chromosome deletion syndrome encompassing the BTK and TIMM8A genes.
abstract: Patients with X-linked agammaglobulinemia (XLA) can present with sensorineural deafness. This can result from a gross deletion that not only involved the Bruton's tyrosine kinase (BTK) gene, but also TIMM8A, mutations in which underlie the Mohr-Tranebjærg syndrome (MTS). We analyzed the genomic break points observed in three XLA-MTS patients and compared these with deletions break points from XLA patients. Patient 1 had a 63-kb deletion with break points in intron 15 of BTK and 4 kb upstream of TAF7L. Patients 2 and 3 had 149.7 and 196 kb deletions comprising BTK, TIMM8A, TAF7L and DRP2. The break points in patients 1 and 3 were located in Alu and endogenous retrovirus (ERV) repeats, whereas the break points in patient 2 did not show involvement of transposable elements. Comparison of gross deletion sizes and involvement of transposable elements in XLA and XLA-MTS patients from the literature showed preferential involvement of Alu elements in smaller deletions (<10 kb). These results show further insights into the molecular mechanisms underlying gross deletions in patients with primary immunodeficiency.
authors.affiliation: Division of Clinical Research, Saitama Children's Medical Center, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Meina
authors.initials: M
authors.lastname: Zhao
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
authors.forename: Takeshi
authors.initials: T
authors.lastname: Futatani
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamada
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oh-ishi
mesh_terms: D000293:Adolescent; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics; D020087:Alu Elements / Q000235:genetics; D002648:Child; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D054062:Deaf-Blind Disorders / Q000235:genetics; D004421:Dystonia / Q000235:genetics; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009896:Optic Atrophy / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D013577:Syndrome; D020079:Terminal Repeat Sequences / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C118122:TIMM8A protein, human; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human