Search results for " pigment"
showing 10 items of 309 documents
The Cellular Function of the Usher Gene Product Myosin VIIa is Specified by Its Ligands
2003
Defects in myosin Vlla are responsible for Usher Syndrome 1B (Weil et al., 1995). Human Usher syndrome (USH), named after the British ophthalmologist Charles Usher (Usher, 1914), is the most common hereditary form of combined blind-and deafness (~ 50% of cases in the developed countries). USH designates a group of clinically and genetically heterogeneous disorders with hearing loss and retinitis pigmentosa (RP). Three different USH types (USH1, 2 and 3; see Table 1) can be distinguished according to the degree of clinical symptomes. USH1 is the most severe subtype, characterized by severe to profound congenital sensorineuronal deafness, constant vestibular dysfunction (balance deficiency) a…
An autosomal dominant retinitis pigmentosa family with close linkage to D7S480 on 7q.
1995
Retinitis pigmentosa is the most prevalent inherited disorder of the retina. It can be autosomal dominant (adRP), autosomal recessive (arRP) or X-linked (XLRP). A form of adRP mapping to chromosome 7q was reported in a large Spanish pedigree. We have typed DNA from the members of another Spanish family for polymorphic markers from the known candidate genes. Positive lod scores were obtained only for the markers located on 7q31-35, giving a maximum lod score of 2.98 (3.01 by multipoint analysis) at theta = 0.00 for D7S480. A brief clinical evaluation is given.
Linkage analysis in Usher syndrome type I (USH1) families from Spain.
1998
Usher syndrome (USH) is an autosomal recessive hereditary disorder characterised by congenital sensorineural hearing loss and gradual visual impairment secondary to retinitis pigmentosa (RP). The disorder is clinically and genetically heterogeneous. With regard to Usher type I (USH1), several subtypes have been described, the most frequent being USH1B located on chromosome 11q13.5. Of 18 USH1 families studied by linkage analysis, 12 (67%) showed significant lod score values for locus D11S527 (Zmax=14.032, theta=0.000) situated on chromosome 11q. Our findings suggest considerable genetic heterogeneity in the Spanish USH1 population. It is important to note that one of our families linked to …
Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability
2004
Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening fo…
Mutations in Myosin VIIA (MYO7A) and Usherin (USH2A) in Spanish patients with usher syndrome types I and II, respectively
2002
Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment and retinitis pigmentosa. Three clinical types are known (USH1, USH2 and USH3), and there is an extensive genetic heterogeneity, with at least ten genes implicated. The most frequently mutated genes are MYO7A, which causes USH1B, and usherin, which causes USH2A. We carried out a mutation analysis of these two genes in the Spanish population. Analysis of the MYO7A gene in patients from 30 USH1 families and sporadic cases identified 32% of disease alleles, with mutation Q821X being the most frequent. Most of the remaining variants are private mutations. With regard to USH2, mutation 2299delG was d…
Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y
2014
Significance Eye, hair, and skin pigmentation are highly variable in humans, particularly in western Eurasian populations. This diversity may be explained by population history, the relaxation of selection pressures, or positive selection. To investigate whether positive natural selection is responsible for depigmentation within Europe, we estimated the strength of selection acting on three genes known to have significant effects on human pigmentation. In a direct approach, these estimates were made using ancient DNA from prehistoric Europeans and computer simulations. This allowed us to determine selection coefficients for a precisely bounded period in the deep past. Our results indicate t…
Molecular Analysis of the Supramolecular Usher Protein Complex in the Retina
2007
Human Usher syndrome (USH) is the most common form of deaf-blindness and also the most frequent case of recessive retinitis pigmentosa. According to the degree of the clinical symptoms, three different types of the Usher syndrome are distinguished: USH1, USH2 and USH3 (Davenport and Omenn, 1977). USH is genetically heterogeneous with eleven chromosomal loci, which can be assigned to the three USH types (USH1A-G, USH2A-C, USH3A) (Petit, 2001). Out of these, USH1 is the most severe form, characterized by profound congenital deafness, constant vestibular dysfunction and prepubertal-onset retinitis pigmentosa. USH2 patients show a milder congenital deafness, a slightly later onset of retinitis …
Estudio genético molecular del síndrome de Usher en España
2005
Usher syndrome (USH) associates deafness and retinitis pigmentosa (RP). It is a disease both clinically and genetically heterogeneous. It is inherited as an autosomal recessive trait and its prevalence makes it the most frequent association of hearing loss and RP. Clinically Usher syndrome is divided into type I (USH1), II (USH2) and III (USH3), according to the severity of hearing loss, age of onset of RP and the existence or not of vestibular dysfunction. There are at least 7 different localizations for USH1 and 5 genes have been identified. For USH2, 3 loci and 2 genes have been reported and USH3 is due to Clarin-1 gene. Our aim is to perform a clinical and genetic characterization of al…
Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments
2004
The most common mutation in the USH2A gene (Usherin), 2299delG, causes both typical Usher (USH) syndrome type II and atypical USH syndrome, two autosomal recessive disorders, characterised by moderate to severe sensorineural hearing loss and retinitis pigmentosa (RP). Furthermore, the C759F mutation in the USH2A gene has been described in 4.5% of patients with nonsyndromic recessive RP. We have investigated the presence of the 2299delG and/or the C759F mutations in 191 unrelated Spanish patients with different syndromic and nonsyndromic retinal diseases, or with nonsyndromic hearing impairment. The 2299delG mutation was observed in patients with clinical signs of USHII or of atypical USH sy…
Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype
2015
The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell’s Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A pheno…