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Contiguous X-chromosome Deletion Syndrome Encompassing the BTK, TIMM8A, TAF7L, and DRP2 Genes

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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.

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Acknowledgements

We wish to thank Dr Zachová and Dr Groh from University Hospital Motol, Prague, Czech Republic and Dr Einberg from Tallinn Children’s Hospital, Estonia taking care for the above-mentioned boys, for their willingness to share data on these patients, and Dr. Chudoba from University Hospital Motol, Prague, for skin fibroblasts cultivation.

This work was supported by The Swedish Science Council, the Wallenberg Foundation, The European Union (EURO-POLICY-PID; SP23-CT-2005-006411), grant MDA 03018774 and grant MSM 0021620812 from the Ministry of Education of the Czech Republic, NIH grant HD17427 and The Jeffrey Modell Foundation.

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Authors and Affiliations

  1. Institute of Immunology, University Hospital Motol, V Uvalu 84, 150 06, Prague 5, Czech Republic

    Anna Šedivá & Aleš Janda

  2. Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden

    C. I. Edvard Smith & A. Charlotta Asplund

  3. Department of Neurology, Thomayer Hospital, Prague, Czech Republic

    Jan Hadač

  4. Centre of Applied Genomics, First Medical Faculty, Charles University, Prague, Czech Republic

    Jiří Zeman, Hana Hansíková, Lenka Dvořáková & Lenka Mrázová

  5. Tallinn Children’s Hospital, Tallinn, Estonia

    Sirje Velbri

  6. Department of Chemistry & Biochemistry, University of California, Los Angeles, USA

    Carla Koehler & Karin Roesch

  7. Department of Pediatrics, University of Pennsylvania, Philadelphia, USA

    Kathleen E. Sullivan

  8. Department of Pediatrics School of Medicine, University of Washington, Seattle, USA

    Takeshi Futatani & Hans D. Ochs

  9. Department of Pediatrics, Toyama Medical and Pharmaceutical University, Toyama, Japan

    Takeshi Futatani

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  1. Anna Šedivá
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Correspondence to Anna Šedivá.

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Šedivá, A., Smith, C.I.E., Asplund, A.C. et al. Contiguous X-chromosome Deletion Syndrome Encompassing the BTK, TIMM8A, TAF7L, and DRP2 Genes. J Clin Immunol 27, 640–646 (2007). https://doi.org/10.1007/s10875-007-9123-x

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  • DOI: https://doi.org/10.1007/s10875-007-9123-x

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