Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference21 articles.
1. Hereditary hearing loss and deafness overview.
https://www.ncbi.nlm.nih.gov/books/NBK1434/
.
2. Hereditary hearing loss homepage.
https://hereditaryhearingloss.org
.
3. Eisenberger T, Di Donato N, Decker C, Delle Vedove A, Neuhaus C, Nurnberg G, Toliat M, Nurnberg P, Murbe D, Bolz HJ. A C-terminal nonsense mutation links PTPRQ with autosomal-dominant hearing loss, DFNA73. Genet Med. 2018;20:614–21.
4. Seifert RA, Coats SA, Oganesian A, Wright MB, Dishmon M, Booth CJ, Johnson RJ, Alpers CE, Bowen-Pope DF. PTPRQ is a novel phosphatidylinositol phosphatase that can be expressed as a cytoplasmic protein or as a subcellularly localized receptor-like protein. Exp Cell Res. 2003;287:374–86.
5. Yu KR, Kim YJ, Jung SK, Ku B, Park H, Cho SY, Jung H, Chung SJ, Bae KH, Lee SC, et al. Structural basis for the dephosphorylating activity of PTPRQ towards phosphatidylinositide substrates. Acta Crystallogr D Biol Crystallogr. 2013;69:1522–9.
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