Disruption of the ATE1 and SLC12A1 genes by balanced translocation in a boy with non-syndromic hearing loss

B. Vona, C. Neuner, N. El Hajj, E. Schneider, R. Farcas, V. Beyer, U. Zechner, A. Keilmann, M. Poot, O. Bartsch, I. Nanda, T. Haaf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

We report on a boy with non-syndromic hearing loss and an apparently balanced translocation t(10;15)(q26.13;q21.1). The same translocation was found in the normally hearing brother, father and paternal grandfather; however, this does not exclude its involvement in disease pathogenesis, for example, by unmasking a second mutation. Breakpoint analysis via FISH with BAC clones and long-range PCR products revealed a disruption of the arginyltransferase 1 (ATE1) gene on translocation chromosome 10 and the solute carrier family 12, member 1 gene (SLC12A1) on translocation chromosome 15. SNP array analysis revealed neither loss nor gain of chromosomal regions in the affected child, and a targeted gene enrichment panel consisting of 130 known deafness genes was negative for pathogenic mutations. The expression patterns in zebrafish and humans did not provide evidence for ear-specific functions of the ATE1 and SLC12A1 genes. Sanger sequencing of the 2 genes in the boy and 180 GJB2 mutation-negative hearing-impaired individuals did not detect homozygous or compound heterozygous pathogenic mutations. Our study demonstrates the many difficulties in unraveling the molecular causes of a heterogeneous phenotype. We cannot directly implicate disruption of ATE1 and/or SLC12A1 to the abnormal hearing phenotype; however, mutations in these genes may have a role in polygenic or multifactorial forms of hearing impairment. On the other hand, it is conceivable that our patient carries a disease-causing mutation in a so far unidentified deafness gene. Evidently, disruption of ATE1 and/or SLC12A1 gene function alone does not have adverse effects.

Original languageEnglish
Pages (from-to)3-10
Number of pages8
JournalMolecular Syndromology
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 2014
Externally publishedYes

Keywords

  • ATE1
  • Disease-associated balanced chromosome rearrangement
  • Non-syndromic hearing impairment
  • Reciprocal translocation
  • SLC12A1

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