title: Disruption of the ATE1 and SLC12A1 Genes by Balanced Translocation in a Boy with Non-Syndromic Hearing Loss.
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.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Vona
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Neuner
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: El Hajj
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schneider
authors.affiliation: Institute of Human Genetics, Department of ORL, University Medical Center, Mainz, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Farcas
authors.affiliation: Institute of Human Genetics, Department of ORL, University Medical Center, Mainz, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Beyer
authors.affiliation: Institute of Human Genetics, Department of ORL, University Medical Center, Mainz, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Zechner
authors.affiliation: Division of Communication Disorders, Department of ORL, University Medical Center, Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Keilmann
authors.affiliation: Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Poot
authors.affiliation: Institute of Human Genetics, Department of ORL, University Medical Center, Mainz, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Bartsch
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Nanda
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Haaf
keywords: ATE1; Disease-associated balanced chromosome rearrangement; Non-syndromic hearing impairment; Reciprocal translocation; SLC12A1