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The Usher syndrome (USH) is a group of autosomalrecessive diseases characterized by congenital sensorineural hearing lossand retinitis pigmentosa. Three clinically distinct forms of Usher syndromehave so far been recognized and can be distinguished from one another by assessingauditory and vestibular function. Usher syndrome type II (USH2) patients havecongenital moderate-to-severe nonprogressive hearing loss, retinitis pigmentosa,and normal vestibular function. Genetic linkage studies have revealed geneticheterogeneity among the three types of USH, with the majority of USH2 familiesshowing linkage to the USH2A locus in 1q41. The USH2A gene (MIM 276901) hasbeen identified: three mutations, 2314delG, 2913delG, and 4353-54delC, wereinitially reported in USH2A patients, the most frequent of which is the 2314delGmutation. It has been reported that this mutation can give rise to typicaland atypical USH2 phenotypes. USH2 cases represent 62% of all USH cases inthe Spanish population, and 95% of these cases have provided evidence of linkageto the USH2A locus. In the present study, the three reported mutations wereanalyzed in 59 Spanish families with a diagnosis of USH type II. The 2314delGwas the only mutation identified in our population: it was detected in 25%of families and 16% of USH2 chromosomes analyzed. This study attempts to estimatethe prevalence of this common mutation in a homogeneous Spanish population. [ABSTRACT FROM AUTHOR]

The Usher syndrome (USH) is an autosomal recessive hereditary disorder characterized by the association of sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. The USH1G gene, encoding SANS, has been found to cause both Usher syndrome type I and atypical Usher syndrome. 109 Spanish unrelated patients suffering from Usher syndrome type I, type II, type III and unclassified Usher syndrome were screened for mutations in this gene, but only eight different changes without a clear pathogenic effect have been detected. Based on these results as well as previous studies in other populations where mutational analysis of this gene has been carried out, one can conclude that USH1G has a minor involvement in Usher syndrome pathogenesis. [ABSTRACT FROM AUTHOR]

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 syndrome, whereas the C759F mutation, regardless of being associated with the 2299delG mutation or not, was identified in cases with nonsyndromic RP, as well as in patients with RP associated with a variability of hearing impairment. The comparative analysis of both phenotypic and genotypic data supports the hypothesis that sensorineural hearing loss in patients with RP may depend on the nature and on the association of the USH2A allele variants present.European Journal of Human Genetics (2004) 12, 407-410. doi:10.1038/sj.ejhg.5201138 Published online 18 February 2004 [ABSTRACT FROM AUTHOR]

Determines whether the mutation causing Usher syndrome type IIa resulted from an ancestral mutational event or represented a mutational hotspot in the disorder locus. Haplotype analysis of DNA samples; Observation of single-nucleotide polymorphisms within the disorder locus; Cause of the widespread geographic distribution of the gene mutation.

The RPGR (retinitis pigmentosa GTPase regulator) gene has been shown to be mutated in 10-20% of patients with X-linked retinitis pigmentosa (XLRP), a severe form of inherited progressive retinal degeneration. A total of 29 different RPGR mutations have been identified in northern European and United States patients. We have performed mutation analysis of the RPGR gene in a cohort of 49 southern European males affected with XLRP. By multiplex SSCA and automatic direct sequencing of all 19 RPGR exons, seven different and novel mutations were identified in eight of the 49 families; these include three splice site mutations, two microdeletions, and two missense mutations. RNA analysis showed that the three splice site defects resulted in the generation of aberrant RPGR transcripts. Six of these mutations were detected in the conserved amino-terminal region of RPGR protein, containing tandem repeats homologous to the RCC1 protein, a guanine nucleotide-exchange factor for RanGTPase. Several exonic and intronic sequence variations were also detected. None of the RPGR mutations reported in other populations were identified in our series. Our results are consistent with the notions of heterogeneity and minority causation of XLRP by mutations in RPGR in Caucasian populations. [ABSTRACT FROM AUTHOR]

Deals with the estimation of the incidence of the fragile X syndrome in Spain. Description of the mutation screening for mutations under FMR-1.