SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR

Amit Kochhar; Dana J Orten; Jessica L Sorensen; Stephanie M Fischer; Cor W R J Cremers; William J Kimberling; Richard J H Smith

doi:10.1002/humu.20714

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SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR

Journal article

Peer reviewed

SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR

Amit Kochhar, Dana J Orten, Jessica L Sorensen, Stephanie M Fischer, Cor W R J Cremers, William J Kimberling and Richard J H Smith

Human mutation, Vol.29(4), pp.565-565

04/2008

DOI: 10.1002/humu.20714

PMID: 18330911

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Abstract

Branchio-oto-renal syndrome (BOR) is a clinically heterogeneous autosomal dominant form of syndromic hearing loss characterized by variable hearing impairment, malformations of the pinnae, the presence of branchial arch remnants, and various renal abnormalities. Both EYA1 and SIX1 are expressed in developing otic, branchial and renal tissue. Consistent with this expression pattern, mutations in both genes cause BOR syndrome. Mutations in EYA1 are found in approximately 40% of patients with the BOR phenotype, however, the role of SIX1 is much lower. To date only three different SIX1 mutations have been described in BOR patients. The current screen of 247 BOR families detected five novel SIX1 mutations (c.50T>A, c.218A>C, c.317T>G, c.329G>A, c.334C>T) and one previously reported mutation (c.328C>T) seen in 5 unrelated families. All mutations are within the protein-binding Six domain. Phenotypic variability was high in these BOR families. Seven of the eight known SIX1 mutations are missense and the one in frame deletion is predicted to be functionally similar. The wide phenotypic variability precludes making genotype-phenotype correlations at this time.

Protein Structure, Tertiary

Amino Acid Sequence

Genetic Testing

Introns

Humans

Middle Aged

Child, Preschool

Molecular Sequence Data

Male

Mutation, Missense

Homeodomain Proteins - chemistry

Homeodomain Proteins - genetics

Sequence Homology, Amino Acid

Phenotype

Protein Tyrosine Phosphatases - genetics

Genes, Dominant

Pedigree

Branchio-Oto-Renal Syndrome - genetics

Adolescent

Female

Nuclear Proteins - genetics

Child

Intracellular Signaling Peptides and Proteins - genetics

Details

Title: Subtitle: SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR
Creators: Amit Kochhar - Doris Duke Clinical Research Fellowship, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
Dana J Orten
Jessica L Sorensen
Stephanie M Fischer
Cor W R J Cremers
William J Kimberling
Richard J H Smith
Resource Type: Journal article
Publication Details: Human mutation, Vol.29(4), pp.565-565
DOI: 10.1002/humu.20714
PMID: 18330911
NLM abbreviation: Hum Mutat
ISSN: 1059-7794
eISSN: 1098-1004
Publisher: United States
Grant note: name: Doris Duke Clinical Research Fellowship (AK), National Institutes of Health, award: NIH-NIDCR 5R01DE014090-04 (WJK), NIH-NIDCD 5R01DC003544-09 (RJHS)
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: 9984007184302771

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