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...

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