A FGF3 mutation associated with differential inner ear malformation, microtia, and microdontia

Reinhard Ramsebner, Martin Ludwig, Thomas Parzefall, Trevor Lucas, Wolf Dieter Baumgartner, Olaf Bodamer, Filiz Basak Cengiz, Christian Schoefer, Mustafa Tekin, Klemens Frei

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Objectives/Hypothesis: Analysis of association between genotype and phenotype. Study Design: Prospective genetic study in a family. Methods: Auditory investigations, computer tomography, and genetic sequencing of the fibroblast growth factor 3 (FGF3) gene were performed on a Somali family presenting with autosomal recessive, hearing impairment, microdontia, and outer ear morphologies ranging from normal auricle development to microtia assessed as type 1 Weerda dysplasia in affected individuals. Results: Computed tomography imaging identified differential inter- and intraindividual malformations of the inner ear including labyrinth aplasia, development of a common cavity to the presence of a cochlear with 1.5 windings (Mondini malformation) in affected individuals, symptoms similar to those described as labyrinth aplasia, microtia, and microdontia (LAMM) syndrome, caused by mutations in FGF3. Genetic sequencing revealed the presence of a novel p.R95W missense mutation in FGF3 segregating with pathology. The p.R95W mutation substitutes a positively charged arginine for a polar tryptophan in the highly conserved RYLAM consensus of the β6 sheet of FGF3 that interacts with FGFR2. Conclusions: These findings describe, for the first time, variable inner ear malformations and outer ear dysplasia in the presence of constant microdontia, associated with homozygous inheritance of the p.R95W mutation in FGF3, mirroring phenotypes observed in mouse models ablating FGF3/FGFR2 signaling.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
Issue number2
StatePublished - Feb 2010
Externally publishedYes


  • FGF3
  • Hearing impairment
  • Labyrinth aplasia
  • Michel aplasia
  • Microdontia
  • Microtia

ASJC Scopus subject areas

  • Otorhinolaryngology


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