Research identifies mutations underlying human hereditary hearing loss

Hereditary hearing loss is the most common sensory disorder in humans. A German research team led by Ingo Kurth from the Institute of Human Genetics at the University Hospital Jena, Germany, used a number of different methods, including Roche’s NimbleGen Custom Sequence Capture 385K array, to identify the gene mutated in the disease locus of the X-chromosome of a Spanish family with hereditary hearing loss.

Targeted enrichment was performed by the German Service Provider ATLAS Biolabs GmbH. In particular, the DNA of two affected males was subjected to target enrichment. Subsequent sequencing analysis at the Cologne Center for Genomics (CCG) resulted in the identification of a total of 3858 and 3443 X-chromosomal variants for each of these two individuals.

Furthermore, a nonsense mutation in the small muscle protein X-linked (SMPX) of the affected individuals had been detected. Nonsense mutations are significant, because they are point mutations in a sequence of DNA that cause a premature stop codon, or a nonsense codon in the transcribed mRNA, resulting in a truncated, incomplete and usually non-functional protein. Based on their findings, the authors propose that long-term maintenance of mechanically stressed inner ear cells critically depends on SMPX function.

The NimbleGen Sequence Capture technology is a sophisticated process for the parallel enrichment of selected genomic regions from complex human genomic DNA. Sequence capture allows enrichment of target regions in a single experiment, replacing the need to perform numerous PCR reactions. The efficiencies of parallel enrichment are a suitable complement for cost-effective, high-throughput, next-generation sequencing.