Branchio-Oto-Renal Syndrome (BOR) is an autosomal dominant disorder which consists of external, middle and inner ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss and renal anomalies. Variable clinical expression between families suggest that multiple gene loci are involved in causing the disease. However, the cause of genetic heterogeneity and clinical variability cannot be resolved until the gene(s) causing BOR syndrome is localized on a chromosome through linkage studies. Thus, the main objective of this genetic study is to map the BOR gene through linkage studies using DNA markers. Initially, four clinically well characterized families will be studied. The DNA from informative individuals will be amplified by Polymerase Chain Reaction using primers near to highly polymorphic dinucleotide repeats. These polymorphisms are distributed widely throughout the human genome. Linkage analysis between these markers and BOR will be done using the LINKAGE (Version 5.04) program. Additional families will be ascertained and tested for linkage with the genes localized in the initial four families. The possibility of genetic heterogeneity will be explored using the program HOMOG and unlinked families will be put through another round of genome searching to determine location of newly discovered genes. Clinical differences between families will be analyzed to determine to what degree they are correlated with different linkage groups. The BOR syndrome results in branchial, auditory, and renal, abnormalities in affected individuals and poses serious health problems. Identification of the BOR gene(s) is the first and foremost step to a more comprehensive understanding of the pathogenesis and etiology of this syndrome. Finding the gene(s) through linkage studies will lay the foundation for further research to isolate and clone such genes for effective treatment and genetic counseling.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Father Flanagan's Boys' Home
Department
Type
DUNS #
City
Boys Town
State
NE
Country
United States
Zip Code
68010
Jaijo, Teresa; Oshima, Aki; Aller, Elena et al. (2012) Mutation screening of the PCDH15 gene in Spanish patients with Usher syndrome type I. Mol Vis 18:1719-26
Malm, Eva; Ponjavic, Vesna; Möller, Claes et al. (2011) Alteration of rod and cone function in children with Usher syndrome. Eur J Ophthalmol 21:30-8
Hmani-Aifa, Mounira; Benzina, Zeineb; Zulfiqar, Fareeha et al. (2009) Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family. Eur J Hum Genet 17:474-82
Tamayo, M L; Lopez, G; Gelvez, N et al. (2008) Genetic counseling in Usher syndrome: linkage and mutational analysis of 10 Colombian families. Genet Couns 19:15-27
Oshima, A; Jaijo, T; Aller, E et al. (2008) Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I. Hum Mutat 29:E37-46
Gopalarao, Deepika; Kimberling, William J; Jesteadt, Walt et al. (2008) Is hearing loss due to mutations in the Connexin 26 gene progressive? Int J Audiol 47:11-20
Cremers, Frans P M; Kimberling, William J; Kulm, Maigi et al. (2007) Development of a genotyping microarray for Usher syndrome. J Med Genet 44:153-60
Yang, Yan-Jun; Wang, Yan-Bo; Lei, Shu-Feng et al. (2007) AHSG gene polymorphisms are associated with bone mineral density in Caucasian nuclear families. Eur J Epidemiol 22:527-32
Chen, Xiang-Ding; Shen, Hui; Recker, Robert R et al. (2006) Linkage exclusion mapping with bone size in 79 Caucasian pedigrees. J Bone Miner Metab 24:337-43
Chen, Xiang-Ding; Shen, Hui; Lei, Shu-Feng et al. (2006) Exclusion mapping of chromosomes 1, 4, 6 and 14 with bone mineral density in 79 Caucasian pedigrees. Bone 38:450-5

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