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K Deffenbacher

Publications and source records attributed to K Deffenbacher.

6 recordsLinked to original sources
PubMed2000

Genomewide search and genetic localization of a second gene associated with autosomal dominant branchio-oto-renal syndrome: clinical and genetic implications.

Branchio-oto-renal (BOR) syndrome is characterized by ear malformations, cervical fistulas, hearing loss, and renal anomalies. It is an autosomal dominant disorder with variable clinical manifestations. The most common features of BOR syndrome are branchial, hearing, and renal anomalies. However, many affected subjects have been observed with branchial-cleft anomalies and hearing loss but without renal anomalies, a condition called "branchio-otic" (BO) syndrome. It is logical to question whether the BOR and BO syndromes are allelic or whether they represent distinct genetic entities. We identified a very large extended family whose members had branchial and hearing anomalies associated with commissural lip pits that segregated in an autosomal dominant fashion. Using a genomewide search strategy, we identified genetic linkage, with a maximum LOD score of 4.81 at recombination fraction 0, between the BO phenotype and polymorphic marker D1S2757 in the genetic region of chromosome 1q31. This is the first report of linkage for a second gene associated with BOR syndrome. The findings have important clinical implications and will provide insight into the genetic basis of BOR syndrome.

Alleles↗
PubMed1999

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

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.

Audiometry↗
PubMedDate not supplied

Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing.

The branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by branchial clefts, preauricular sinuses, hearing loss, and renal anomalies. The BOR gene, EYA1, on chromosome 8q13 has recently been cloned and mutations have been identified. In this study, we have analyzed the sites of mutations in the EYA1 gene in BOR patients to determine the spectrum of mutations. We have identified two missense mutations and have compared all the mutations reported to date in the EYA1 gene. In total, 20 mutations have been described, the majority of which are clustered in the carboxy-terminal region of the gene. The clinical features of the BOR individuals have also been compared to determine if the nature of the mutation correlates with the type and severity of the clinical symptoms. Most of the mutations arose de novo and, other than the clustering in carboxy-terminal exons 9-16, no mutation hot spots have been identified. These results provide the basis for molecular genetic testing that will help in the clinical evaluation and genetic counseling of members of BOR families.

Base Sequence↗