FOXI1 – Pendred Syndrome

Limited sequencing of the FOXI1 transcription factor gene in cohorts with Pendred syndrome has identified only rare heterozygous missense variants without evidence of biallelic involvement or clear segregation. In a study of 68 patients with monoallelic SLC26A4 mutations, one individual carried FOXI1 c.367C>T (p.Arg123Trp) but no familial co-segregation was observed and the variant frequency was consistent with a benign polymorphism (PMID:23965030). Another series detected FOXI1 c.716C>T (p.Pro239Leu) in a single case, yet functional assays demonstrated intact transcriptional activation of SLC26A4 (PMID:22285650). Large multicentre and targeted NGS panels failed to implicate FOXI1 as a significant contributor to Pendred syndrome or nonsyndromic enlarged vestibular aqueduct, with diagnostic yields attributable overwhelmingly to SLC26A4 and other loci (PMID:30268946; PMID:38833161).

References

• Audiology & neuro-otology • 2010 • Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome. PMID:19648736
• BMC medical genetics • 2013 • Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in Pendred syndrome/enlarged vestibular aqueducts. PMID:23965030
• Molecular and cellular endocrinology • 2012 • Molecular and functional studies of 4 candidate loci in Pendred syndrome and nonsyndromic hearing loss. PMID:22285650
• The Journal of molecular diagnostics : JMD • 2019 • Targeted Next-Generation Sequencing Facilitates Genetic Diagnosis and Provides Novel Pathogenetic Insights into Deafness with Enlarged Vestibular Aqueduct. PMID:30268946
• Neuroradiology • 2024 • Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study. PMID:38833161

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