Identification of a novel isoform of Slc26a4 by single-cell RNA-sequencing of pendrin-expressing cells in the cochlea

Pathogenic variation of SLC26A4 gene causes both Pendred syndrome (PDS) and non-syndromic enlarged vestibular aqueduct (NSEVA/DFNB4), two autosomal recessive disorders. The former accounts for approximately 6% of human genetic hearing loss, making it the second most common form of syndromic deafness after Usher syndrome, while the latter is the most common radiological malformation associated with childhood...

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No immediate practice change — this is a basic-science genetic discovery that may eventually inform genetic counseling and diagnosis for Pendred syndrome and DFNB4, but has no direct clinical application yet.

Identifying a novel SLC26A4 isoform improves understanding of the molecular basis of Pendred syndrome and non-syndromic enlarged vestibular aqueduct, potentially opening new avenues for genetic diagnosis and future therapeutic targets.

1. 01A novel isoform of the Slc26a4 gene was identified using single-cell RNA sequencing of cochlear cells.
2. 02Slc26a4 encodes pendrin, a protein critical for inner ear fluid balance; mutations cause Pendred syndrome and DFNB4 hearing loss.
3. 03Single-cell RNA sequencing allowed precise identification of pendrin-expressing cell populations in the cochlea.
4. 04Findings published in Human Genetics, a peer-reviewed genetics journal.
5. 05Discovery may refine genetic testing panels and explain previously unresolved cases of SLC26A4-related hearing loss.

PMID

42461329

DOI

10.1007/s00439-026-02858-x.

Journal

Human Genetics

Publication type

research_article

Evidence level

2b

Population

Pendrin-expressing cells in the cochlea (animal or in-vitro model implied by single-cell RNA sequencing methodology)

Intervention

Single-cell RNA sequencing of pendrin-expressing cochlear cells