Genetic heterogeneity associated with branchio-oto-renal syndrome

Kumar, Shrawan; Kimberling, William J.; Marres, H.A.M.; Cremers, C.W.R.J.

doi:10.1002/(sici)1096-8628(19990319)83:3<207::aid-ajmg12>3.0.co;2-a

Cited by 8 publications

(8 citation statements)

References 15 publications

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“…Twenty mutations have so far been described in the EYA1 gene (encompassing 16 exons) in BO/BOR families (Abdelhak et al 1997a;Abdelhak et al 1997b;Kumar et al 1997/98;Kumar et al 1998a;Kumar et al 1998b;Vincent et al 1997). …”

Section: Discussionmentioning

confidence: 99%

“…According to the BO/BOR classification, the father's condition corresponded with BOR syndrome and the two affected childrens' with BO syndrome. It is noteworthy that the same mutation in the responsible gene could cause various conditions, although other reported mutations in the EYA1 gene may also lead to a wide range of phenotypic expression (Kumar et al 1998b;Vincent et al 1997). Recently, genetic heterogeneity associated with branchial and hearing anomalies has also been reported (Kumar et al 1998b;Stratakis et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Prevalence of the BOR syndrome has been estimated as 1 : 40,000, and therefore may account for as much as 2%-3% of profound hearing loss in children (Fraser et al 1980). Recent advances in molecular genetics have revealed that the gene responsible for BOR syndrome is localized in 8q Smith et al 1992), and that there were various mutations in the EYA1 gene, the human homologue of the Drosophila eyes absent gene, in Northern European and other BOR patients (Abdelhak et al 1997a;Abdelhak et al 1997b;Kumar et al 1997/98;Kumar et al 1998a;Kumar et al 1998b).…”

Section: Introductionmentioning

confidence: 99%

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EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family

et al. 1999

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Advances in molecular genetics have recently revealed that mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome in European and other populations. This is the first report confirming that an EYA1 gene mutation is also disease-causing in an Asian population. We have described one Japanese BOR syndrome family showing a novel mutation in exon 7 of the EYA1 gene. There was extensive variation of clinical phenotypes within this family. When the physician is confronted with a BOR family showing a wide variation in clinical expression, molecular genetic testing helps to achieve accurate diagnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family

et al. 1999

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“…In humans, mutations in EYA1 and its interacting partners SIX1 and SIX5 have been identified as causing BOR syndrome (Abdelhak et al, 1997; Ruf et al, 2004; Hoskins et al, 2007). This syndrome has a wide intrafamilial variability and reduced penetrance (Kumar et al, 1999). A closely related disorder is branchio-oto (BO) syndrome, where patients suffer from branchial defects and deafness without renal abnormalities (OMIM 602588), but might be a milder variant of BOR syndrome.…”

Section: Introductionmentioning

confidence: 99%

Catweasel mice: A novel role for Six1 in sensory patch development and a model for branchio-oto-renal syndrome

Bosman

Quint

Fuchs

et al. 2009

Developmental Biology

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Large-scale mouse mutagenesis initiatives have provided new mouse mutants that are useful models of human deafness and vestibular dysfunction. Catweasel is a novel N-ethyl-N-nitrosourea (ENU)-induced mutation. Heterozygous catweasel mutant mice exhibit mild headtossing associated with a posterior crista defect. We mapped the catweasel mutation to a critical region of 13 Mb on chromosome 12 containing the Six1, -4 and -6 genes. We identified a basepair substitution in exon 1 of the Six1 gene that changes a conserved glutamic acid (E) at position 121 to a glycine (G) in the Six1 homeodomain. Cwe/Cwe animals lack Preyer and righting reflexes, display severe headshaking and have severely truncated cochlea and semicircular canals. Cwe/Cwe animals had very few hair cells in the utricle, but their ampullae and cochlea were devoid of any hair cells. Bmp4, Jag1 and Sox2 expression were largely absent at early stages of sensory development and NeuroD expression was reduced in the developing vestibulo-acoustic ganglion. Lastly we show that Six1 genetically interacts with Jag1. We propose that the catweasel phenotype is due to a hypomorphic mutation in Six1 and that catweasel mice are a suitable model for branchio-oto-renal syndrome. In addition Six1 has a pivotal role in early sensory patch development and may act in the same genetic pathway as Jag1.

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“…However, currently available methods of screening, including direct nucleotide sequencing, fail to identify mutations in more than 70% of families in which the diagnosis of BOR syndrome has been made clinically. In some of these families, linkage to 8q13 cannot be demonstrated, suggesting genetic heterogeneity [9]. Recently, a second gene that is probably implicated in the development of BOR syndrome has been mapped to chromosome 1q31 [10].…”

Section: Introductionmentioning

confidence: 99%

Branchio-oto-renal syndrome: identification of a novel mutation in the EYA1 gene

Rodríguez‐Soriano

Vallo

Bilbao

et al. 2001

Pediatric Nephrology

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Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the association of branchial cysts or fistulae, external ear malformation and/or preauricular pits, hearing loss, and renal anomalies. Mutations in the EYA1 gene, a human homologue of the Drosophila 'eyes absent' gene, have been identified as cause of the syndrome. We report here two families with BOR syndrome. In one family, with the complete phenotype, a novel splice site mutation in exon 15 (1599 +1 G to A) is described. No mutations in the EYA1 gene were found in a second family presenting with ear pits, deafness, and renal anomalies, but lacking branchial fistulae. These and other findings from the literature suggest the existence of genetic heterogeneity of the BOR, BO, and other related phenotypes, with two or more genes involved.

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Genetic heterogeneity associated with branchio-oto-renal syndrome

Cited by 8 publications

References 15 publications

EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family

EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family

Catweasel mice: A novel role for Six1 in sensory patch development and a model for branchio-oto-renal syndrome

Branchio-oto-renal syndrome: identification of a novel mutation in the EYA1 gene

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