First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene

Autor: Peter Nürnberg, Monika Ołdak, Nataliya Di Donato, Dominika Oziębło, Grażyna Tacikowska, Hanno J. Bolz, Marcin L. Leja, Henryk Skarżyński, Birgit Budde, Anna Sarosiak
Rok vydání: 2019
Předmět:
0301 basic medicine
Proband
Male
lcsh:Medicine
Translational Research
Biomedical
Exon
0302 clinical medicine
Age of Onset
Child
Exome sequencing
PTPRQ
Genes
Dominant
Sanger sequencing
Genetics
Linkage
Receptor-Like Protein Tyrosine Phosphatases
Class 3
General Medicine
Middle Aged
Pedigree
Phenotype
030220 oncology & carcinogenesis
symbols
Female
medicine.symptom
Adult
Heterozygote
Adolescent
Hearing loss
Hearing Loss
Sensorineural
Biology
Polymorphism
Single Nucleotide
General Biochemistry
Genetics and Molecular Biology
DNA sequencing
03 medical and health sciences
symbols.namesake
Young Adult
Genetic linkage
medicine
Humans
Dominant
Pathogenic
Research
lcsh:R
Peptide Chain Termination
Translational
030104 developmental biology
Mutation
Next-generation sequencing
Mutant Proteins
Poland
Age of onset
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-7 (2019)
ISSN: 1479-5876
0011-4502
Popis: Background Biallelic PTPRQ pathogenic variants have been previously reported as causative for autosomal recessive non-syndromic hearing loss. In 2018 the first heterozygous PTPRQ variant has been implicated in the development of autosomal dominant non-syndromic hearing loss (ADNSHL) in a German family. The study presented the only, so far known, PTPRQ pathogenic variant (c.6881G>A) in ADNSHL. It is located in the last PTPRQ coding exon and introduces a premature stop codon (p.Trp2294*). Methods A five-generation Polish family with ADNSHL was recruited for the study (n = 14). Thorough audiological, neurotological and imaging studies were carried out to precisely define the phenotype. Genomic DNA was isolated from peripheral blood samples or buccal swabs of available family members. Clinical exome sequencing was conducted for the proband. Family segregation analysis of the identified variants was performed using Sanger sequencing. Single nucleotide polymorphism array on DNA samples from the Polish and the original German family was used for genome-wide linkage analysis. Results Combining clinical exome sequencing and family segregation analysis, we have identified the same (NM_001145026.2:c.6881G>A, NP_001138498.1:p.Trp2294*) PTPRQ alteration in the Polish ADNSHL family. Using genome-wide linkage analysis, we found that the studied family and the original German family derive from a common ancestor. Deep phenotyping of the affected individuals showed that in contrast to the recessive form, the PTPRQ-related ADNSHL is not associated with vestibular dysfunction. In both families ADNSHL was progressive, affected mainly high frequencies and had a variable age of onset. Conclusion Our data provide the first confirmation of PTPRQ involvement in ADNSHL. The finding strongly reinforces the inclusion of PTPRQ to the small set of genes leading to both autosomal recessive and dominant hearing loss.
Databáze: OpenAIRE
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