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

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 149
Author(s):  
María Domínguez-Ruiz ◽  
Montserrat Rodríguez-Ballesteros ◽  
Marta Gandía ◽  
Elena Gómez-Rosas ◽  
Manuela Villamar ◽  
...  

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.

2019 ◽  
Vol 27 (9) ◽  
pp. 1456-1465 ◽  
Author(s):  
Imen Chakchouk ◽  
Di Zhang ◽  
Zhihui Zhang ◽  
Laurent C. Francioli ◽  
Regie Lyn P. Santos-Cortez ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Rongqun Zhai ◽  
Haifeng Feng ◽  
Qingli Li ◽  
Wei Lu ◽  
Danhua Liu ◽  
...  

Objective. To analyze the phenotypic features and pathogenic variants of three unrelated families presenting with nonsyndromic auditory neuropathy spectrum disorder (ANSD). Methods. Three recruited families that were affected by congenital deafness were clinically evaluated, including a detailed family history and audiological and radiological examination. The peripheral blood of all patients and their parents was collected for DNA extraction, and then, the exonic and flanking regions were enriched and sequenced using targeted capture and high-throughput sequencing technology. Bioinformatics analyses and the Sanger sequencing were carried out to screen and validate candidate pathogenic variants. The pathogenicity of candidate variants was evaluated by an approach that was based on the standards and guidelines for interpreting genetic variants as proposed by the American College of Medical Genetics and Genomics (ACMG). Results. Four patients in three families were diagnosed as nonsyndromic ANSD, and all exhibited OTOF gene mutations. Among them, two individuals in family 1 (i.e., fam 1-II-2 and fam 1-II-3) carried homozygous variants c.[2688del];[2688del] (NM_194248.3). Two individuals from family 2 (fam 2-II-1) and family 3 (fam 3-II-4) carried compound heterozygous variants c.[4960G>A];[1469C>G] and c.[2675A>G];[2977_2978del], respectively. Conclusions. Three unrelated pedigrees with ANSD were caused by pathogenic variants in the OTOF gene. Five mutations were found and included c.2688del, c.2675A>G, c.2977_2978del, c.4960G>A, and c.1469C>G, of which the first two are novel and expanded mutational spectrum of the OTOF gene, thus having important implications for genetic counseling of the family.


2021 ◽  
Vol 11 (4) ◽  
pp. 609-617
Author(s):  
Francesca Forli ◽  
Luca Bruschini ◽  
Beatrice Franciosi ◽  
Roberta Battini ◽  
Gemma Marinella ◽  
...  

Perrault syndrome (PRLTS) is a rare autosomal recessive disorder characterised by ovarian failure in females and sensorineural hearing loss (SNHL) in both genders. In the present paper we describe a child affected by PRLTS3, due to CLPP homozygous mutations, presenting auditory neuropathy spectrum disorder (ANSD) with bilateral progressive SNHL. This is the first case reported in the literature of an ANSD in PRLTS3. CLPP is a nuclear encoded mitochondrial protease directed at the mitochondrial matrix. It is encoded on chromosome 19. This protease participates in mitochondrial protein quality control by degrading misfolded or damaged proteins, thus maintaining the normal metabolic function of the cell. In PRLTS3, the peptidase activity of CLPP is suppressed. Neurological impairments involved in PRLTS3 suggest that the pathogenic mutations in CLPP might trigger a mitochondrial dysfunction. A comprehensive description of the clinical and audiological presentation, as well as the issues related to cochlear implant (CI) procedure and the results, are addressed and discussed. A brief review of the literature on this topic is also provided.


2021 ◽  
Vol 42 (5) ◽  
pp. 103057
Author(s):  
Firas Sbeih ◽  
Donald M. Goldberg ◽  
Sara Liu ◽  
Maxwell Y. Lee ◽  
Gina Stillitano ◽  
...  

2020 ◽  
Vol 129 ◽  
pp. 109757 ◽  
Author(s):  
Joseph B. Meleca ◽  
Gina Stillitano ◽  
Maxwell Y. Lee ◽  
Whitney Lyle ◽  
Yi-Chun Carol Liu ◽  
...  

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