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. 2020 Jul 1:2020:6137083.
doi: 10.1155/2020/6137083. eCollection 2020.

Four Novel Variants in POU4F3 Cause Autosomal Dominant Nonsyndromic Hearing Loss

Tian-Yi Cui  1   2   3   4 , Xue Gao  5 , Sha-Sha Huang  1   2   3 , Yan-Yan Sun  6 , Si-Qi Zhang  6 , Xin-Xia Jiang  6 , Yan-Zhong Yang  6 , Dong-Yang Kang  1   2   3 , Qing-Wen Zhu  6 , Yong-Yi Yuan  1   2   3
Affiliations

Four Novel Variants in POU4F3 Cause Autosomal Dominant Nonsyndromic Hearing Loss

Tian-Yi Cui et al. Neural Plast. .

Abstract

Hereditary hearing loss is one of the most common sensory disabilities worldwide. Mutation of POU domain class 4 transcription factor 3 (POU4F3) is considered the pathogenic cause of autosomal dominant nonsyndromic hearing loss (ADNSHL), designated as autosomal dominant nonsyndromic deafness 15. In this study, four novel variants in POU4F3, c.696G>T (p.Glu232Asp), c.325C>T (p.His109Tyr), c.635T>C (p.Leu212Pro), and c.183delG (p.Ala62Argfs∗22), were identified in four different Chinese families with ADNSHL by targeted next-generation sequencing and Sanger sequencing. Based on the American College of Medical Genetics and Genomics guidelines, c.183delG (p.Ala62Argfs∗22) is classified as a pathogenic variant, c.696G>T (p.Glu232Asp) and c.635T>C (p.Leu212Pro) are classified as likely pathogenic variants, and c.325C>T (p.His109Tyr) is classified as a variant of uncertain significance. Based on previous reports and the results of this study, we speculated that POU4F3 pathogenic variants are significant contributors to ADNSHL in the East Asian population. Therefore, screening of POU4F3 should be a routine examination for the diagnosis of hereditary hearing loss.

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Conflict of interest statement

There are no financial relationships with any organizations that might have an interest in the submitted work, and there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1
Pedigree, temporal bone CT, variant analysis, and audiogram of family A. (a) Affected subjects are denoted in black. Arrow shows the proband. (b) Temporal bone CT of the III:3 shows no structural change. (c) Chromatogram shows POU4F3 heterozygous c.696G>T detected in patients. (d) Audiograms of the affected subjects. Hearing loss appears to be highly heterogeneous (red: right ear; blue: left ear).
Figure 2
Figure 2
Pedigree, temporal bone CT, variant analysis, and audiogram of family B. (a) Affected subjects are denoted in black. Arrow shows the proband. (b) Temporal bone CT of the III:1 shows no structural change. (c) Chromatogram shows POU4F3 heterozygous c.325C>T detected in patients. (d) Audiograms of the affected subjects. Hearing loss appears to involve high frequency (red: right ear; blue: left ear).
Figure 3
Figure 3
Pedigree, temporal bone CT, variant analysis, and audiogram of family C. (a) Affected subjects are denoted in black. Arrow shows the proband. (b) Temporal bone CT of the IV:2 shows no structural change. (c) Chromatogram shows POU4F3 heterozygous c.635T>C detected in patients. (d) Audiograms of the affected subjects. Audiogram configuration of IV:2 was U-shaped. Downsloping audiogram configurations were observed in III:6 and II:4 (red: right ear; blue: left ear).
Figure 4
Figure 4
Pedigree, temporal bone CT, variant analysis, and audiogram of family D. (a) Affected subjects are denoted in black. Arrow shows the proband. (b) Temporal bone CT of the III:2 shows no structural change. (c) Chromatogram shows POU4F3 heterozygous c.183delG detected in patients. (d) Audiograms of the affected subjects (red: right ear; blue: left ear).
Figure 5
Figure 5
Protein structure of POU4F3 and conservation analysis. (a) Domain structure of POU4F3 showing the localization of four variants identified in this study. (b) Protein alignment showing that POU4F3 p.His109Tyr, p.Leu212Pro, and p.Glu232Asp all occur at evolutionarily conserved amino acids (shown by the red triangle) across 10 species.
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