Disruption of the ATE1 and SLC12A1 Genes by Balanced Translocation in a Boy with Non-Syndromic Hearing Loss

Molecular Syndromology

A. Keilmann¹  T. Haaf¹  N. El Hajj¹  R. Farcas¹  B. Vona¹  V. Beyer¹  C. Neuner¹  O. Bartsch¹  E. Schneider¹  I. Nanda¹  U. Zechner¹  M. Poot¹ 

[1] aInstitute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany

关键词: ATE1;    Disease-associated balanced chromosome rearrangement;    Non-syndromic hearing impairment;    Reciprocal translocation;    SLC12A1
;   

DOI  :  10.1159/000355443

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

Unknown