Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR

Dana J Orten; Stephanie M Fischer; Jessica L Sorensen; Uppala Radhakrishna; Cor W R J Cremers; Henri A M Marres; Guy Van Camp; Katherine O Welch; Richard J H Smith; William J Kimberling

doi:10.1002/humu.20691

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Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR

Journal article

Peer reviewed

Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR

Dana J Orten, Stephanie M Fischer, Jessica L Sorensen, Uppala Radhakrishna, Cor W R J Cremers, Henri A M Marres, Guy Van Camp, Katherine O Welch, Richard J H Smith and William J Kimberling

Human mutation, Vol.29(4), pp.537-544

04/2008

DOI: 10.1002/humu.20691

PMID: 18220287

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Abstract

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by the association of branchial and external ear malformations, hearing loss, and renal anomalies. The phenotype varies from ear pits to profound hearing loss, branchial fistulae, and kidney agenesis. The most common gene mutated in BOR families is EYA1, a transcriptional activator. Over 80 different disease-causing mutations have been published (www.healthcare.uiowa.edu/labs/pendredandbor/, last accessed 20 November 2007). We analyzed the EYA1 coding region (16 exons) from 435 families (345 at the University of Iowa [UI] and 95 at Boys Town National Research Hospital [BTNRH], including five at both) and found 70 different EYA1 mutations in 89 families. Most of the mutations (56/70) were private. EYA1 mutations were found in 31% of families (76/248) fitting established clinical criteria for BOR and 7% of families with questionable BOR phenotype (13/187). Severity of the phenotype did not correlate with type of mutation nor with the domain involved. These results add considerably to the spectrum of EYA1 mutations associated with BOR and indicate that the BOR phenotype is an indication for molecular studies to diagnose EYA1-associated BOR.

Amino Acid Sequence

Frameshift Mutation

Exons

Humans

Molecular Sequence Data

Male

Mutation, Missense

Case-Control Studies

Sequence Homology, Amino Acid

Phenotype

Protein Tyrosine Phosphatases - genetics

Genes, Dominant

DNA Mutational Analysis

Branchio-Oto-Renal Syndrome - genetics

RNA Splicing - genetics

Female

Polymorphism, Single Nucleotide

Mutation

Nuclear Proteins - genetics

Intracellular Signaling Peptides and Proteins - genetics

Details

Title: Subtitle: Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR
Creators: Dana J Orten - Department of Genetics, Boys Town National Research Hospital, Omaha, Nebraska 68164, USA
Stephanie M Fischer
Jessica L Sorensen
Uppala Radhakrishna
Cor W R J Cremers
Henri A M Marres
Guy Van Camp
Katherine O Welch
Richard J H Smith
William J Kimberling
Resource Type: Journal article
Publication Details: Human mutation, Vol.29(4), pp.537-544
DOI: 10.1002/humu.20691
PMID: 18220287
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Grant note: 5R01DE014090-04 / NIDCR NIH HHS 5R01DC003544-09 / NIDCD NIH HHS 5R01DC04293 / NIDCD NIH HHS
Language: English
Date published: 04/2008
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006403902771

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