RESUMO
Usher syndrome is an autosomal recessive condition characterized by sensorineural hearing loss, variable vestibular dysfunction, and visual impairment due to retinitis pigmentosa (RP). The seven proteins that have been identified for Usher syndrome type 1 (USH1) and type 2 (USH2) may interact in a large protein complex. In order to identify novel USH genes, we followed a candidate strategy, assuming that mutations in proteins interacting with this "USH network" may cause Usher syndrome as well. The DFNB31 gene encodes whirlin, a PDZ scaffold protein with expression in both hair cell stereocilia and retinal photoreceptor cells. Whirlin represents an excellent candidate for USH2 because it binds to Usherin (USH2A) and VLGR1b (USH2C). Genotyping of microsatellite markers specific for the DFNB31 gene locus on chromosome 9q32 was performed in a German USH2 family that had been excluded for all known USH loci. Patients showed common haplotypes. Sequence analysis of DFNB31 revealed compound heterozygosity for a nonsense mutation, p.Q103X, in exon 1, and a mutation in the splice donor site of exon 2, c.837+1G>A. DFNB31 mutations appear to be a rare cause of Usher syndrome, since no mutations were identified in an additional 96 USH2 patients. While mutations in the C-terminal half of whirlin have previously been reported in non-syndromic deafness (DFNB31), both alterations identified in our USH2 family affect the long protein isoform. We propose that mutations causing Usher syndrome are probably restricted to exons 1-6 that are specific for the long isoform and probably crucial for retinal function. We describe a novel genetic subtype for Usher syndrome, which we named USH2D and which is caused by mutations in whirlin. Moreover, this is the first case of USH2 that is allelic to non-syndromic deafness.
Assuntos
Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Mutação , Retinose Pigmentar/genética , Síndromes de Usher/genética , Adulto , Análise Mutacional de DNA , Feminino , Ligação Genética , Genótipo , Humanos , Masculino , Proteínas de Membrana/química , Repetições de Microssatélites , Linhagem , Isoformas de Proteínas , Síndromes de Usher/metabolismoRESUMO
Cylindrical specimens may be tested advantageously by using grazing-incidence interferometry. A multiple positions test in combination with rotational averaging has recently been used to separate the surface deviations of the specimen from the interferometric aberrations. To reduce the measuring time and to check whether the results are reliable, a second procedure is now investigated, which uses the principle of the multiple positions test to determine quantities proportional to the difference quotients of the surface deviations. After numerical integration, the results can be compared with those obtained previously by rotational averaging. The measurement principle is described, and calibration results are presented.
RESUMO
Interferometry in grazing incidence can be used to test cylindrical mantle surfaces. The absolute accuracy of the resulting surface profiles is limited by systematic wavefront aberrations caused in the interferometer, in particular due to an inversion of the test wavefront in an interferometer using diffractive beam splitters. For cylindrical specimens, a calibration method using four positions has therefore been investigated. This test is combined with another method of optical metrology: the rotational averaging procedure. The implementation for grazing incidence is described and measurement results for hollow cylinders are presented. The gain in accuracy is demonstrated.