Clinical Diagnostics Service – Genetic Deafness

Molecular Otolaryngology Research Laboratories

EYA1

The Clinical Diagnostics Service of the Molecular Otolaryngology Research Laboratories is a Joint Commission-approved CLIA-accredited diagnostic laboratory that offers mutation screening of several genes.

Branchio-Oto-Renal Syndrome (OMIM# 113650)

   EYA1 was identified as the gene that causes Branchio-Oto-Renal (BOR) syndrome (OMIM# 113650) by Abdelhak and colleagues in 1997. Characteristics of this syndrome include branchial anomalies, deafness, preauricular tags and/or pits, external, middle and/or inner ear anomalies and renal anomalies. Multiple family studies have shown this dominant syndrome is incompletely penetrant with variable expressivity, meaning that phenotypic variation is seen between families and within families. The estimated prevalence of BOR syndrome is 1:40,000; it affects about 2% of profoundly deaf children (Fraser, 1980.)

EYA1

   The gene, EYA1 (OMIM# 601653), contains 16 exons and encodes the 559 amino acid protein EYA1 (Eyes Absent 1). In animal studies, Xu and colleagues have shown that EYA1 controls critical inductive signaling events in ear and kidney formation. Over 50 mutations have been identified in EYA1 including missense, nonsense, splice site and complex mutations involving large deletions or chromosomal mutations. Current estimates suggest that 20% of BOR syndrome is caused by large deletions or chromosomal mutations in EYA1. There is no single common mutation. MORL offers a clinical screen to detect missense, nonsense or small deletions/insertions within an exon.

MORL screening methodology

   Screening for EYA1 is performed via DHPLC and sequencing. Oligonucleotide primers have been designed to amplify each exon. Amplified samples are run on the DHPLC; abnormal elution profiles are sequenced to determine the specific mutation.

DHPLC profile of EYA1 Exon 8

Legend: Profiles in brown and black contain mutations; profile in purple is wild type

Sensitivity

   Sensitivity is greater than 98%.

Turn-around time

   Turn around time is approximately 3 months.

Cost: $500

Indications for screening

   Screening should be considered in persons with a phenotype consistent with the diagnosis of BOR syndrome (Chang et al., 2004).

GeneTests GeneReviews - Branchiootorenal Syndrome

References

Abdelhak, S. et al.: A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nature Genet. 15: 157-164, 1997.
PubMed ID : 9020840

Fraser, F. C. et al.: Frequency of the branchio-oto-renal (BOR) syndrome in children with profound hearing loss. Am. J. Med. Genet. 7: 341-349, 1980.
PubMed ID : 7468659

Stratakis, C. A. et al.: Description of a large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss, and ear pits, and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3). Am. J. Med. Genet. 79: 209-214, 1998.
PubMed ID : 9788564

Chang, E. H. et al.: Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences. Hum. Mutat. 23: 582-589, 2004.
PubMed ID : 15146463

Pendred and BOR Homepage: http://www.medicine.uiowa.edu/pendredandbor/