A novel mutation in POU3F4 in a Chinese family with X-linked non-syndromic hearing loss

Abstract

ObjectiveBased on the clinical manifestations of a hearing loss patient, the POU3F4 gene was tested for diagnosis of etiology.MethodsA comprehensive physical examination was performed on the proband to exclude abnormalities of other organs, and detailed audiological testing and temporal bone CT scan were also performed. Genomic DNA was extracted using the proband's peripheral blood leukocytes. Polymerase chain reactions (PCR) were performed in the coding sequence of the POU3F4 gene. Direct DNA sequencing was subsequently applied to screen the entire coding region of the POU3F4 gene.ResultsThe proband had severe sensorineural hearing loss. Temporal CT showed bilateral cochlear incomplete partition, vestibule dysplasia, internal auditory canal fundus expansion, and cochlear interlink with the internal auditory canal fundus. A novel mutation (c.530C > A (p.S177X)) in the POU3F4 gene was found in this patient, creating an new stop codon and was predicted to result in a truncated protein lacking normal POU3F4 transcription factor function.ConclusionThrough analysis of the POU3F4 gene and clinical manifestations in the patient, we conclude that a novel mutation may have resulted in a premature stop codon, contributing to the mutation of POU3F4 gene.

Considering gene therapy to protect from X‐linked deafness DFNX2 and associated neurodevelopmental disorders

“…POU superfamily genes are involved in cell proliferation and differentiation during organogenesis. 97 Little is known about how POU3F4 mutations induce hearing loss, except that some of them induce subcellular mislocalization of the protein, 15 , 29 , 34 while others lead to the production of a truncated protein, 7 , 11 , 13 , 15 , 22 , 23 , 28 , 29 , 40 or they may affect the structure of the protein and impair DNA binding ability. 7 , 15 , 19 , 29 , 30 In other cases, deletions upstream of POU3F4 that remove noncoding cis‐regulatory elements are likely to affect gene expression.…”

“…To date, over 80 deafness‐causative mutations in the coding sequence of POU3F4 have been identified in some 20 countries, including missense, nonsense, deletion, frameshift, and extension mutations (Figure 1). 6–46 Moreover, deletions of the entire gene as well as deletions, paracentric inversions, and duplications upstream of the gene (containing the putative regulatory elements of POU3F4 transcription) were also reported 12,13,24,47–52 . X‐linked deafness type 2 (DFNX2, locus Xq21.1), caused by POU3F4 mutations, accounts for nearly 50% of all cases of X‐linked hearing loss.…”

“… 5 , 6 To date, over 80 deafness‐causative mutations in the coding sequence of POU3F4 have been identified in some 20 countries, including missense, nonsense, deletion, frameshift, and extension mutations (Figure 1 ). 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 Moreover, deletions of the entire gene as well as deletions, paracentric inversions, and duplications upstream of the gene (containing the putative regulatory elements of POU3F4 transcription) were also reported. 12 , 13 , 24 , 47 , 48 , 49 , 50 ...…”

X-Linked Sensorineural Hearing Loss: A Literature Review

“…X-linked hearing loss type 2 (DFNX2) is found in ~50% of all families carrying X-linked non-syndromic hearing loss [87, 88]. The most frequent clinical features of DFNX2 in affected males are: hypoplasia of cochlea, enlarged internal acoustic canal and a characteristic stapes gusher upon surgery and stapes fixation [89, 90].…”

A novel POU domain class 3 transcription factor 4 mutation causes X-linked non-syndromic hearing loss in a Chinese family

“…[7] All reports on POU3F4 mutants in Chinese families demonstrated no penetrance in the carrier female members. [8,9] In this study, a novel non-sense mutation is identified in POU3F4 gene in a Chinese family with X-linked non-syndromic HL. Based on the results of molecular diagnosis and the clinical data, we provided genetic counseling for the family members.…”