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. 2022 Jan 15;13(1):149.
doi: 10.3390/genes13010149.

Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder

María Domínguez-Ruiz  1   2 , Montserrat Rodríguez-Ballesteros  1   2 , Marta Gandía  1   2 , Elena Gómez-Rosas  1   2 , Manuela Villamar  1   2 , Pietro Scimemi  3   4 , Patrizia Mancini  5 , Nanna D Rendtorff  6 , Miguel A Moreno-Pelayo  1   2 , Lisbeth Tranebjaerg  6   7 , Carme Medà  8 , Rosamaria Santarelli  3   4 , Ignacio Del Castillo  1   2
Affiliations

Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder

María Domínguez-Ruiz et al. Genes (Basel). .

Abstract

Pathogenic variants in the PJVK gene cause the DFNB59 type of autosomal recessive non-syndromic hearing impairment (AR-NSHI). Phenotypes are not homogeneous, as a few subjects show auditory neuropathy spectrum disorder (ANSD), while others show cochlear hearing loss. The numbers of reported cases and pathogenic variants are still small to establish accurate genotype-phenotype correlations. We investigated a cohort of 77 Spanish familial cases of AR-NSHI, in whom DFNB1 had been excluded, and a cohort of 84 simplex cases with isolated ANSD in whom OTOF variants had been excluded. All seven exons and exon-intron boundaries of the PJVK gene were sequenced. We report three novel DFNB59 cases, one from the AR-NSHI cohort and two from the ANSD cohort, with stable, severe to profound NSHI. Two of the subjects received unilateral cochlear implantation, with apparent good outcomes. Our study expands the spectrum of PJVK mutations, as we report four novel pathogenic variants: p.Leu224Arg, p.His294Ilefs*43, p.His294Asp and p.Phe317Serfs*20. We review the reported cases of DFNB59, summarize the clinical features of this rare subtype of AR-NSHI and discuss the involvement of PJVK in ANSD.

Keywords: DFNB59; PJVK; auditory neuropathy spectrum disorder; genetic epidemiology; non-syndromic hearing impairment; pejvakin.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Novel pathogenic variants that were found in this study. (a) Pedigrees showing the segregation of variants. (b) Electropherograms from subject S269 II:1 (left panel) and from subject E1471 II:1 (right panel). (c) Alignment of pejvakin orthologous sequences from human and nine other vertebrates. Asterisks indicate identical residues across all sequences; colons, conserved positions (residues of strongly similar properties); periods, semi-conserved positions (residues of weakly similar properties). Sequence accesion numbers: Homo sapiens (NP_001036167.1); Gorilla gorilla (XP_004032916.1); Bos taurus (NP_001180112.1); Canis lupus (XP_535979.2); Mus musculus (NP_001074180.1); Monodelphis domestica (XP_001368857.1); Gallus gallus (XP_426573.2); Python bivittatus (XP_007433246.1); Xenopus tropicalis (XP_012826511.1); Danio rerio (XP_009300492.1).
Figure 2
Figure 2
Audiograms from subjects with PJVK variants causing sensorineural hearing loss. Only results for air conduction are shown. Red line, right ear. Blue line, left ear. (a,b) Subject S269 II:1 at ages 7 yr and 14 yr, respectively. (c,d) Subject S269 II:2 at ages 5 yr and 11 yr, respectively. (e) Subject E1471 II:1, while using hearing aids in both ears (red and blue lines); black line, unaided hearing. (f) Subject E1471 II:1, while using the cochlear implant in the right ear (red line) and a hearing aid in the left ear (blue line); black line, unaided hearing. (g) Subject DAN07 II:1 at age 12 yr, before unilateral cochlear implantation.
See this image and copyright information in PMC

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