Related Experiment Video
Updated: Feb 1, 2026
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
Genotyping and audiological characteristics of infants with a single-allele SLC26A4 mutation
Xuelei Zhao1, Lihui Huang1, Xueyao Wang1
1Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing, China; Key Laboratory of Otolaryngology, Head and Neck Surgery, Ministry of Education, Beijing, China.
Insights
This study found that 3.50% of infants with a single SLC26A4 gene mutation also carried a second-allele variant, with 2.96% having pathogenic mutations. Bi-allelic mutations often result in severe to profound hearing loss.
Area of Science:
- Genetics
- Audiology
- Otolaryngology
Background:
- The SLC26A4 gene is crucial for inner ear development and function.
- Mutations in SLC26A4 are a significant cause of hereditary hearing loss.
- Identifying second-allele variants is important for understanding genotype-phenotype correlations.
Purpose of the Study:
- To determine the frequency of second-allele variants in infants with a known single SLC26A4 mutation.
- To investigate the audiological characteristics of infants with bi-allelic SLC26A4 mutations.
Main Methods:
- Sequencing of the SLC26A4 gene in 371 infants with a single-allele mutation.
- Audiological evaluation for patients with bi-allelic mutations.
- Imaging studies (CT/MRI) were performed on some patients.
Main Results:
- A second-allele variant was identified in 3.50% of patients (2.96% pathogenic).
- Bi-allelic SLC26A4 mutations were associated with hearing loss in 11 out of 13 infants.
- Hearing loss ranged from severe to profound, with a sloping configuration.
Conclusions:
- The frequency of second-allele variants in SLC26A4 mutations is 3.50% in this Chinese cohort.
- Bi-allelic SLC26A4 mutations typically lead to severe-to-profound hearing loss.
- Further research is needed on the pathogenicity of specific variants like c.757A>G.
Objectives:
To identify second-allele variant in infants with a known single-allele mutation of the SLC26A4 gene and to determine the frequency of their occurrence; and to investigate the clinical audiological characteristics of infants with bi-allelic mutations in SLC26A4.
Methods:
The study subjects were 371 patients with a single-allele SLC26A4 mutation detected by neonatal deafness gene screening (4 genes and 9 pathogenic variants) who were treated at the otology outpatient department of Beijing Tongren Hospital. The exonic and flanking splice site regions of the SLC26A4 gene were sequenced for all patients. All patients with bi-allelic SLC26A4 mutations underwent audiological evaluation, and some also underwent temporal bone computed tomography and/or inner ear magnetic resonance imaging.
Results:
Of the 371 patients, 314 (84.64%) had an c.919-2A > G heterozygous mutation and 57 (15.36%) had a c.2168A > G (p.H723R) heterozygous mutation. 13 patients (3.50%) had a second-allele variant, including 11 (2.96%) with pathogenic mutations and 1 (0.27%) with a likely benign variant. Of the 13 patients with bi-allelic mutations, 11 had hearing loss and 2 had normal hearing, the latter of whom had c.919-2A > G/c.1766A > G and c.919-2A > G/c.757A > G compound heterozygous mutations, respectively. Four of the 13 patients with bi-allelic mutations had passed the universal newborn hearing screening, including 2 cases (15.38%) with hearing loss. The most prevalent degree of hearing loss was profound (40.91%), followed by severe (36.36%). The most prevalent audiometric configuration was sloping hearing loss (50.00%), followed by flat-type hearing loss (40.91%).
Conclusions:
This is the first report in China of the frequency of occurrence of second-allele variant in infants with a known single-allele mutation of the SLC26A4 gene; the frequency was 3.50% for any type of variant and 2.96% for pathogenic mutations. A novel variant, c.1766A > G (p.Q589R), which is likely benign, was identified. The pathogenicity of c.757A > G (p.I253V) mutation deserves more in-depth research. For infants with bi-allelic SLC26A4 mutations, the degree of hearing loss was mainly severe-to-profound and the audiometric configuration was mainly sloping.
Related Concept Videos
01:49Multiple Allele Traits
01:39Mutations
01:09Mutation, Gene Flow, and Genetic Drift
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
00:36Viral Mutations