title: Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L, and DRP2 genes.
abstract: X-linked agammaglobulinemia (XLA) is characterized by low levels of B-lymphocytes with early-onset, recurrent, microbial infections occasionally causing neurological symptoms. We observed an atypical clinical course of XLA, complicated since early childhood with neurological impairment, progressive sensorineural deafness, and dystonia in six boys of four unrelated families. The neurologic symptoms suggested the diagnosis of Mohr-Tranebjaerg syndrome, caused by mutations in the TIMM8A gene, previously known as DDP1, and located centromerically of BTK. Deafness dystonia peptide (DDP1) participates in neurological development and is a part of the mitochondrial protein import pathway. Mutation analysis of the BTK gene revealed gross deletions of different lengths in all patients, in one case extending approximately 196 kb, including the genes TIMM8A, TAF7L, and DRP2. The most prominent clinical findings of this contiguous deletion syndrome are the combination of immunodeficiency and sensorineural deafness, which were present in all affected boys. The severity of symptoms, however, did not correlate with the extent of the deletion.
authors.affiliation: Institute of Immunology, University Hospital Motol, V Uvalu 84, 150 06, Prague 5, Czech Republic. anna.sediva@fnmotol.cz
authors.forename: Anna
authors.initials: A
authors.lastname: Sedivá
authors.forename: C I Edvard
authors.initials: CI
authors.lastname: Smith
authors.forename: A Charlotta
authors.initials: AC
authors.lastname: Asplund
authors.forename: Jan
authors.initials: J
authors.lastname: Hadac
authors.forename: Ales
authors.initials: A
authors.lastname: Janda
authors.forename: Jirí
authors.initials: J
authors.lastname: Zeman
authors.forename: Hana
authors.initials: H
authors.lastname: Hansíková
authors.forename: Lenka
authors.initials: L
authors.lastname: Dvoráková
authors.forename: Lenka
authors.initials: L
authors.lastname: Mrázová
authors.forename: Sirje
authors.initials: S
authors.lastname: Velbri
authors.forename: Carla
authors.initials: C
authors.lastname: Koehler
authors.forename: Karin
authors.initials: K
authors.lastname: Roesch
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
authors.forename: Takeshi
authors.initials: T
authors.lastname: Futatani
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
mesh_terms: D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D015331:Cohort Studies; D003937:Diagnosis, Differential; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics*; D035362:Transcription Factor TFIID / Q000235:genetics*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009419:Nerve Tissue Proteins; C091537:TAF7 protein, human; D035381:TATA-Binding Protein Associated Factors; C118122:TIMM8A protein, human; D035362:Transcription Factor TFIID; C095114:collapsin response mediator protein-2; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D012319:RNA Polymerase II