Diagnostics Service of the Molecular
Otolaryngology & Renal Research Laboratories is a Joint
Commission-approved CLIA-accredited diagnostic laboratory that offers
mutation screening of several genes.
Branchio-Oto-Renal Syndrome (OMIM# 113650)
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
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
Oligonucleotide primers have been designed for amplification of each exon
including intron/exon boundaries of EYA1. These amplimers
are used for bi-directional sequencing.
Sensitivity is greater than 98%.
Turn around time is approximately 3 months (Average
TAT - 53 days).
Indications for screening
Screening should be considered in persons with a
phenotype consistent with the diagnosis of BOR syndrome (Chang et al., 2004).
– Branchiootorenal Syndrome
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,
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