Usher syndrome is a hereditary disorder causing congenital hearing loss, progressive retinitis pigmentosa, and vestibular dysfunction. At least two genetic types of Usher syndrome are known to exist. Usher type I (USH1) is characterized by a profound hearing loss and absent vestibular responses; type II (USH2) has a milder hearing loss and normal vestibular responses. The USH2 gene has been localized to chromosome 1. The task ahead is to find and clone the USH2 gene. Based on preliminary results, USH2 lies within 14.8 cMo of chromosome 1q32-1q42 probably between D1S70 and D1S81/PPOL. There are no other DNA polymorphisms, nor any candidate genes, in that region. Thus, new DNA polymorphisms must be developed for this 'clone poor' region. DNA libraries specific to the bands within chromosome segment 1q32-1q42 will be isolated using chromosome microdissection and restriction fragment recovery by PCR from GTG banded chromosomes. Physical positions of clones will be verified by somatic cell analysis and valid clones will be screened for short tandem repeat polymorphisms (i.e dinucleotide repeats). A saturation map of the region will be constructed using the new polymorphisms and the USH2 gene will be positioned within the updated 1q32-1q42 map. The objective of this project is to reduce the localization region to 0.5 to 1.0 cMo. About 1 out of 20,000 individuals is affected with Usher syndrome. The burden caused by loss of the two most vital human senses is tremendous. It isolates patients from the mainstream of the society resulting in severe psychological stress and reduces their ability to act independently. The answers to many intriguing questions regarding Usher Syndrome will not be available until the gene is cloned. The understanding of the etiology of Usher syndrome will provide critical information about the underlying mechanisms of function and expression of the gene(s). Such knowledge has important implications for genetic counseling and effective treatment.
| 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 |
| 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 |
| 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 |
| 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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