SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct
Abstract Background Recessive mutations of coding regions and splice sites of the SLC26A4 gene cause hearing loss with enlargement of the vestibular aqueduct (EVA). Some patients also have a thyroid iodination defect that can lead to multinodular goiter as part of Pendred syndrome. A haplotype of va...
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| Format: | Article |
| Language: | English |
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BMC
2019-07-01
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| Series: | BMC Medical Genetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12881-019-0853-4 |
| _version_ | 1819069260807274496 |
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| author | Janet R. Chao Parna Chattaraj Tina Munjal Keiji Honda Kelly A. King Christopher K. Zalewski Wade W. Chien Carmen C. Brewer Andrew J. Griffith |
| author_facet | Janet R. Chao Parna Chattaraj Tina Munjal Keiji Honda Kelly A. King Christopher K. Zalewski Wade W. Chien Carmen C. Brewer Andrew J. Griffith |
| author_sort | Janet R. Chao |
| collection | DOAJ |
| description | Abstract Background Recessive mutations of coding regions and splice sites of the SLC26A4 gene cause hearing loss with enlargement of the vestibular aqueduct (EVA). Some patients also have a thyroid iodination defect that can lead to multinodular goiter as part of Pendred syndrome. A haplotype of variants upstream of SLC26A4, called CEVA, acts as a pathogenic recessive allele in trans to mutations affecting the coding regions or splice sites of SLC26A4. Our first hypothesis is that CEVA, acting as a pathogenic recessive allele, is correlated with a less severe phenotype than mutations affecting the coding regions and splice sites of SLC26A4. Our second hypothesis is that CEVA acts as a modifier of the phenotype in patients with EVA caused by mutations affecting the coding regions or splice sites of both alleles of SLC26A4 or EVA caused by other factors. Methods This was a prospective cohort study of 114 individuals and 202 ears with EVA. To test our first hypothesis, we compared the thyroid and auditory phenotypes of subjects with mutations affecting coding regions of both alleles of SLC26A4 with those of subjects carrying CEVA in trans to mutations affecting the coding regions. To test our second hypothesis, we compared the phenotypes associated with the presence versus absence of CEVA among subjects with no coding region mutations, as well as among subjects with mutations affecting coding regions of both alleles. Results Subjects carrying CEVA in trans to a mutation of SLC26A4 have a normal thyroid phenotype and less severe hearing loss in comparison to individuals with mutations affecting coding regions of both alleles of SLC26A4. In subjects with no mutant alleles of SLC26A4, hearing loss was more severe in subjects who carry the CEVA haplotype in comparison to non-carriers. There was no correlation of CEVA with the phenotype of subjects with mutations affecting coding regions of both alleles. Conclusions CEVA, acting as a likely pathogenic recessive allele, is associated with a less severe phenotype than alleles with a mutation affecting the coding regions or splice sites of SLC26A4. CEVA may act as a genetic modifier in patients with EVA caused by other factors. |
| first_indexed | 2024-12-21T16:47:13Z |
| format | Article |
| id | doaj.art-a1762e3b69644b61a4f412a1d20d7f56 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-21T16:47:13Z |
| publishDate | 2019-07-01 |
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| series | BMC Medical Genetics |
| spelling | doaj.art-a1762e3b69644b61a4f412a1d20d7f562022-12-21T18:56:58ZengBMCBMC Medical Genetics1471-23502019-07-012011610.1186/s12881-019-0853-4SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueductJanet R. Chao0Parna Chattaraj1Tina Munjal2Keiji Honda3Kelly A. King4Christopher K. Zalewski5Wade W. Chien6Carmen C. Brewer7Andrew J. Griffith8Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthNeurotology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthOtolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of HealthAbstract Background Recessive mutations of coding regions and splice sites of the SLC26A4 gene cause hearing loss with enlargement of the vestibular aqueduct (EVA). Some patients also have a thyroid iodination defect that can lead to multinodular goiter as part of Pendred syndrome. A haplotype of variants upstream of SLC26A4, called CEVA, acts as a pathogenic recessive allele in trans to mutations affecting the coding regions or splice sites of SLC26A4. Our first hypothesis is that CEVA, acting as a pathogenic recessive allele, is correlated with a less severe phenotype than mutations affecting the coding regions and splice sites of SLC26A4. Our second hypothesis is that CEVA acts as a modifier of the phenotype in patients with EVA caused by mutations affecting the coding regions or splice sites of both alleles of SLC26A4 or EVA caused by other factors. Methods This was a prospective cohort study of 114 individuals and 202 ears with EVA. To test our first hypothesis, we compared the thyroid and auditory phenotypes of subjects with mutations affecting coding regions of both alleles of SLC26A4 with those of subjects carrying CEVA in trans to mutations affecting the coding regions. To test our second hypothesis, we compared the phenotypes associated with the presence versus absence of CEVA among subjects with no coding region mutations, as well as among subjects with mutations affecting coding regions of both alleles. Results Subjects carrying CEVA in trans to a mutation of SLC26A4 have a normal thyroid phenotype and less severe hearing loss in comparison to individuals with mutations affecting coding regions of both alleles of SLC26A4. In subjects with no mutant alleles of SLC26A4, hearing loss was more severe in subjects who carry the CEVA haplotype in comparison to non-carriers. There was no correlation of CEVA with the phenotype of subjects with mutations affecting coding regions of both alleles. Conclusions CEVA, acting as a likely pathogenic recessive allele, is associated with a less severe phenotype than alleles with a mutation affecting the coding regions or splice sites of SLC26A4. CEVA may act as a genetic modifier in patients with EVA caused by other factors.http://link.springer.com/article/10.1186/s12881-019-0853-4DeafnessDFNB4HaplotypeHearingNoncodingPendred syndrome |
| spellingShingle | Janet R. Chao Parna Chattaraj Tina Munjal Keiji Honda Kelly A. King Christopher K. Zalewski Wade W. Chien Carmen C. Brewer Andrew J. Griffith SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct BMC Medical Genetics Deafness DFNB4 Haplotype Hearing Noncoding Pendred syndrome |
| title | SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct |
| title_full | SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct |
| title_fullStr | SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct |
| title_full_unstemmed | SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct |
| title_short | SLC26A4-linked CEVA haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct |
| title_sort | slc26a4 linked ceva haplotype correlates with phenotype in patients with enlargement of the vestibular aqueduct |
| topic | Deafness DFNB4 Haplotype Hearing Noncoding Pendred syndrome |
| url | http://link.springer.com/article/10.1186/s12881-019-0853-4 |
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