Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM

Hum Genet. 2001 May;108(5):398-403. doi: 10.1007/s004390100495.


Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder involving hearing loss, branchial defects, ear pits and renal abnormalities. Oto-facio-cervical (OFC) syndrome is clinically similar to BOR syndrome, with clinical features in addition to those of BOR syndrome. Mutations in the EYA1 gene (localised to 8q13.3) account for nearly 70% of BOR syndrome cases exhibiting at least three of the major features. Small intragenic deletions of the 3' region of the gene have also been reported in patients with BOR syndrome. We have developed a fluorescent quantitative multiplex polymerase chain reaction for three 3' exons (7, 9 and 13) of the EYA1 gene. This dosage assay, combined with microsatellite marker analysis, has identified de novo deletions of the EYA1 gene and surrounding region in two patients with complex phenotypes involving features of BOR syndrome. One patient with OFC syndrome carried a large deletion of the EYA1 gene region, confirming that OFC syndrome is allelic with BOR syndrome. Microsatellite analysis has shown that comparison of the boundaries of this large deletion with other reported rearrangements of the region reduces the critical region for Duane syndrome (an eye movement disorder) to between markers D8S553 and D8S1797, a genetic distance of approximately 1 cM.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Alleles*
  • Branchio-Oto-Renal Syndrome / genetics*
  • Branchio-Oto-Renal Syndrome / physiopathology
  • DNA Mutational Analysis
  • Duane Retraction Syndrome / genetics*
  • Exons / genetics
  • Female
  • Genetic Linkage / genetics*
  • Genetic Testing
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Microsatellite Repeats / genetics
  • Nuclear Proteins
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Protein Tyrosine Phosphatases
  • Sequence Deletion / genetics*
  • Trans-Activators / genetics*


  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • EYA1 protein, human
  • Protein Tyrosine Phosphatases