Universität zu Köln

Ozieblo, Dominika ORCID: 0000-0002-3454-8002, Sarosiak, Anna ORCID: 0000-0003-0806-9195, Leja, Marcin L., Budde, Birgit S., Tacikowska, Grazyna ORCID: 0000-0002-5570-7092, Di Donato, Nataliya ORCID: 0000-0001-9439-4677, Bolz, Hanno J., Nurnberg, Peter, Skarzynski, Henryk and Oldak, Monika ORCID: 0000-0002-4216-9141 (2019). First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene. J. Transl. Med., 17 (1). LONDON: BMC. ISSN 1479-5876

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ozieblo, Dominika UNSPECIFIED orcid.org/0000-0002-3454-8002 UNSPECIFIED Sarosiak, Anna UNSPECIFIED orcid.org/0000-0003-0806-9195 UNSPECIFIED Leja, Marcin L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Budde, Birgit S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tacikowska, Grazyna UNSPECIFIED orcid.org/0000-0002-5570-7092 UNSPECIFIED Di Donato, Nataliya UNSPECIFIED orcid.org/0000-0001-9439-4677 UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nurnberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Skarzynski, Henryk UNSPECIFIED UNSPECIFIED UNSPECIFIED Oldak, Monika UNSPECIFIED orcid.org/0000-0002-4216-9141 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-130301
DOI:	10.1186/s12967-019-2099-5
Journal or Publication Title:	J. Transl. Med.
Volume:	17
Number:	1
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1479-5876
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-TYROSINE-PHOSPHATASE; INOSITOL LIPID PHOSPHATASE; NONSENSE MUTATION; MYOSIN-VI; RECEPTOR; IDENTIFICATION; STEREOCILIA; END Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13030