Omics · study · 2026
A Novel LMX1A Frameshift Variant Underlies Familial Phenotypic Heterogeneity in DFNA7
Listed in NCBI GEO
Hereditary hearing loss (HHL) exhibits significant genetic heterogeneity, with mutations in LMX1A related to autosomal dominant non-syndromic hearing loss (DFNA7).
Description
Here, we report a novel heterozygous frameshift variant, LMX1A c.405delT (p. Phe135LeufsTer3) in a three-generation Chinese family with progressive and asymmetric sensorineural hearing loss (ASNHL).
Clinical evaluations revealed variable severity (mild-to-profound) and onset (infancy to mid-adulthood), with cochlear aperture stenosis observed in the proband. Whole exon sequencing (WES), Sanger sequencing and segregation analysis confirmed the novel mutation and its cosegregation with the phenotype. Structural modeling predicted that truncation within the conserved LIM2 domain disrupts protein function.
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Functional studies demonstrated reduced transcriptional activity, supporting haploinsufficiency as the pathogenic mechanism. RNA sequencing (RNA-seq) of HEI-OC1 cells revealed dysregulation of neurodevelopmental, synaptic and mitochondrial pathways, implicating neurodegeneration and metabolic dysfunction in LMX1A-related hearing loss. This study highlights the role of LMX1A in auditory homeostasis, provides insights into genotype-phenotype correlations and underscores structural cochlear anomalies as potential contributors to ASNHL.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299979 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299979 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1277803 ncbi.nlm.nih.gov/bioproject/PRJNA1277803 ↗
project · from NCBI GEO
- PubMed 42253511 pubmed.ncbi.nlm.nih.gov/42253511 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Genetics 70% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE299979 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (70%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |