A human homologue of the Drosophila eyes absent gene underlies Branchio-Oto-Renal (BOR) syndrome and identifies a novel gene family

Abstract

A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

Xeya3 regulates survival and proliferation of neural progenitor cells within the anterior neural plate of Xenopus embryos

“…In vertebrates, it has been demonstrated that EYA1/2 and SIX1 interact physically and are expressed in sensorial placodes as well as in the developing kidney. Consistently, mutations in either Eya1 or Six1 underlie the branchio-oto-renal (BOR) syndrome, which is characterized by anomalies of face, ear, and kidneys (Abdelhak et al, 1997;Ruf et al, 2004;Kozlowski et al, 2005). Furthermore, EYA2 cooperates with SIX1 and DACH2 to regulate muscle development (Heanue et al, 1999), and reported activities of EYA3 in cell culture depend on the presence of SIX1 (Li et al, 2003).…”

Development of the zebrafish inner ear

“…Loss of cristae; abnormal maculae, semicircular canal system and neurogenesis; cell death (Whitfield et al, 1996;Kozlowski et al, in preparation) Eya1 bor (Johnson et al, 1999); targeted disruption (Xu et al, 1999) Branchio-Oto-Renal syndrome (Abdelhak et al, 1997) jekyll (jek) ugdh1 (Walsh and Stainier, 2001) UDP-glucose dehydrogenase (sugarless)…”

HPPD: A newly recognized autosomal dominant disorder involving hypertelorism, preauricular sinus, punctal pits, and deafness mapping to chromosome 14q31

“…Patients with BOR/BO syndrome may have conductive, sensorineural, or mixed type hearing loss which may be stable or progressive with severity ranging from mild to profound [Fraser et al, 1980]. To date, mutations in three genes, EYA1 [Abdelhak et al, 1997], SIX1 [Ruf et al, 2004;Ito et al, 2006], and SIX5 [Hoskins et al, 2007], have been found in patients with BOR/BO syndrome.…”