Delayed progressive sensorineural hearing loss due to a novel compound heterozygous PTPRQ mutation in a Chinese patient

Abstract

Background:The Protein tyrosine phosphatase receptor Q (PTPRQ) gene encodes a member of the type III receptor-like protein tyrosine phosphatase family found in the stereocilium. Mutations in PTPRQ are mostly associated with deafness, autosomal recessive type 84 (DFNB 84), which usually results in progressive familial hearing loss. Methods: A 25-year-old woman and her sister, both with postlingual-delayed progressive sensorineural hearing loss, were examined. They were from a nonconsanguineous marriage and had no family history of hearing loss. New compound heterozygous PTPRQ gene mutations, nonsense (c.90C > A, p.Y30X) and splice (c.5426 + 1G > A) mutations in two PTPRQ alleles, were identified in the two sisters and were presumably autosomal recessive. The c.90C > A (p.Y30X) mutation was mapped to exon 2 of PTPRQ (NM_001145026). Results: The c.90C > A mutation leads to a premature stop codon and a truncated protein. The c.5426 + 1G > A mutation leads to a truncated protein lacking the extracellular domain. Hence, both mutations were predicted to be pathogenic, leading to a deficiency of the extracellular, transmembrane, and phosphatase domains because of nonsense-mediated mRNA degradation.Conclusions: This study increases the spectrum of PTPRQ gene mutations that might be involved in delayed progressive autosomal recessive non-syndromic hearing loss.

Detailed Clinical Features of PTPRQ-Associated Hearing Loss Identified in a Large Japanese Hearing Loss Cohort

“…This variant resulted in the truncation of the protein by escaping nonsense-mediated mRNA decay and exerted a dominant-negative effect [23]. On the other hand, the loss of function variants identified in other exons were reported as causative for autosomal recessive HL (DFNB84) [7,23]. All variants identified in this study were located in exon 3 to exon 39 and no variants were located in exon 45.…”

“…The PTPRQ gene encodes a member of the type III receptor-like protein tyrosine phosphatase family, and PTPRQ is known as one of the causative genes for non-syndromic SNHL without inner malformation. PTPRQ-associated HL is a relatively rare genetic cause of HL, with only about 30 causative PTPRQ variants reported to cause SNHL [7]. In this study, we identified 17 variants from 13 HL patients, which is the largest number of patients yet to be detected.…”

“…In addition, excluding only one case, all patients showed onset HL in their first decade. In previous reports, most patients with autosomal recessive inheritance also had congenital or prelingual HL [7,[36][37][38][39][40][41][42]. Three cases of autosomal recessive PTPRQ-associated HL with post-lingual HL were reported in a single previous report (exact ages unknown) [28].…”

“…His high frequency hearing then deteriorated from moderate to profound over 20 years, with his HL changing from flat-type to high-frequency steeply sloping HL. In previous studies, the hearing level in the patients with autosomal recessive inheritance ranged from moderate to profound [7,[28][29][30][31][32][33][34][35]. Most patients had progressive, high-frequency HL regardless of autosomal recessive or autosomal dominant inheritance [7,23,28,[37][38][39][40][41][42][43].…”

“…PTPRQ is a relatively rare causative gene for SNHL. To date, about 30 causative PTPRQ variants have been reported to cause SNHL [7]. However, the detailed clinical features of PTPRQassociated HL remain unclear.…”