The Application of Next-Generation Sequencing for Mutation Detection in Autosomal-Dominant Hereditary Hearing Impairment.
Otol Neurotol
; 38(6): 900-903, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28419064
ABSTRACT
OBJECTIVE:
Identification of the causative mutation using next-generation sequencing in autosomal-dominant hereditary hearing impairment, as mutation analysis in hereditary hearing impairment by classic genetic methods, is hindered by the high heterogeneity of the disease. PATIENTS Two Swiss families with autosomal-dominant hereditary hearing impairment. INTERVENTION Amplified DNA libraries for next-generation sequencing were constructed from extracted genomic DNA, derived from peripheral blood, and enriched by a custom-made sequence capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq instrument, 300 cycles and paired-end sequencing. Technical data analysis was performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The detection of mutations in genes related to hearing loss by next-generation sequencing was subsequently confirmed using specific polymerase-chain-reaction and Sanger sequencing. MAIN OUTCOMEMEASURE:
Mutation detection in hearing-loss-related genes.RESULTS:
The first family harbored the mutation c.5383+5delGTGA in the TECTA-gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG in the WFS1-gene and a second mutation TCOF1-c.1028G>A were identified.CONCLUSION:
Next-generation sequencing successfully identified the causative mutation in families with autosomal-dominant hereditary hearing impairment. The results helped to clarify the pathogenic role of a known mutation and led to the detection of a novel one. NGS represents a feasible approach with great potential future in the diagnostics of hereditary hearing impairment, even in smaller labs.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Análisis Mutacional de ADN
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Secuenciación de Nucleótidos de Alto Rendimiento
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Pérdida Auditiva Sensorineural
Tipo de estudio:
Diagnostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Año:
2017
Tipo del documento:
Article