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

Abstract

BackgroundBiallelic 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*).MethodsA 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.ResultsCombining 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.ConclusionOur 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.

[Retracted] Identification of Hearing Loss‐Associated Variants of PTPRQ, MYO15A, and SERPINB6 in Pakistani Families

“…PTPRQ , located at chromosome 21q21.31, encodes the protein tyrosine phosphatase receptor Q (EC 3.1.1.48), a member of the protein tyrosine phosphatase receptor family type III. Previously, variants in PTPRQ have been reported for having dominant (DFNA73) [ 21 ], as well as recessively inherited (DFNB84) forms of nonsyndromic HL in human [ 22 , 23 ]. We identified a novel splice variant (c.55-2A>G) of PTPRQ inherited in a recessive manner in family GCFHL-01.…”

The role of next generation sequencing in predicting hearing loss

“…In our Institute, we have successfully implemented highthroughput DNA sequencing methods to resolve the genetic background of HL. Results of genetic testing provide information on the cause of HL and help to identify family members being at risk of developing HL [12]. They are also indispensable for delivering an accurate diagnosis, correctly directing further diagnostic and treatment procedures, and predicting the development of a syndromic form of HL when other clinical findings are not apparent [13].…”

Early onset adult deafness in the Rhodesian Ridgeback dog is associated with an in-frame deletion in the EPS8L2 gene

“…However, there are also known cases of pigmentation-unrelated congenital deafness in some breeds, including Doberman Pinschers [ 16 – 18 ] and Labrador Retrievers [ 14 ]. Independent identification of putative causal mutations in a gene PTPRQ in dogs and humans [ 19 , 20 ] emphasizes the importance of dogs as a model system for studying naturally occurring hearing loss.…”