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Aller E, Jaijo T, Oltra S, Alió J, Galán F, Nájera C, Beneyto M, Millán JM. Mutation screening ofUSH3gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.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 namedclarin-1and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations inclarin-1gene among our series of Usher syndrome Spanish patients.Clarin-1has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II. [ABSTRACT FROM AUTHOR]

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been previously described as a possible prognostic marker in normal karyotype acute myeloid leukemia (AML) patients. Nevertheless, the findings in this field are not always reproducible in different series. One hundred and seventy-five adult de novo AML patients were screened with two different methods for the detection of SNP rs16754: high-resolution melting (HRM) and FRET hybridization probes. Direct sequencing was used to validate both techniques. The SNP was detected in 52 out of 175 patients (30 %), both by HRM and hybridization probes. Direct sequencing confirmed that every positive sample in the screening methods had a variation in the DNA sequence. Patients with the wild-type genotype (WT1(AA)) for the SNP rs16754 were significantly younger than those with the heterozygous WT1(AG) genotype. No other difference was observed for baseline characteristic or outcome between patients with or without the SNP. Both techniques are equally reliable and reproducible as screening methods for the detection of the SNP rs16754, allowing for the selection of those samples that will need to be sequenced. We were unable to confirm the suggested favorable outcome of SNP rs16754 in de novo AML.

Introduction: The information offered by the new genomic and proteomic techniques will play a central role in our knowledge of cancer; but it is limited by the lack of available tissue samples. Cancer in children is a sum of infrequent diseases, so tumor banks are support tools for translational research, providing access to a sufficiently large series of samples, which would minimize the asymmetric effect of the diverse origin., Material and Methods: From 2003 a Molecular Pathology Network in Pediatric Solid Tumors Netwoks exists in Spain, and we are a part of it. Our aim was to create a pediatric tumor bank program and consensus documents about its use., Results: Standard Operating Procedures for collection and transport of samples have been created., Conclusions: Thinking about the fast progress in Molecular Biology and the low frequency in pediatric tumors, it is vital to consider the importance of a bio bank.

Mutations in USH2A gene have been shown to be responsible for Usher syndrome type II, an autosomal recessive disorder characterised by hearing loss and retinitis pigmentosa. USH2A was firstly described as consisting of 21 exons, but 52 novel exons at the 3' end of the gene were recently identified. In this report, a mutation analysis of the new 52 exons of USH2A gene was carried out in 32 unrelated patients in which both disease-causing mutations could not be found after the screening of the first 21 exons of the USH2A gene. On analysing the new 52 exons, fourteen novel mutations were identified in 14 out of the 32 cases studied, including 7 missense, 5 frameshift, 1 duplication and a putative splice-site mutation.

Usher syndrome type I is the most severe form of Usher syndrome. It is an autosomal recessive disorder characterized by profound congenital sensorineural deafness, retinitis pigmentosa, and vestibular abnormalities. Mutations in the myosin VIIA gene (MYO7A) are responsible for Usher syndrome type 1B (USH1B). This gene is thought to bear greatest responsibility for USH1 and, depending on the study, has been reported to account for between 24% and 59% of USH1 cases. In this report a mutation screening of the MYO7A gene was carried out in a series of 48 unrelated USH1 families using single strand conformation polymorphism analysis (SSCP) and direct sequencing of those fragments showed an abnormal electrophoretic pattern. Twenty-five mutations were identified in 23 out of the 48 families studied (47.9%). Twelve of these mutations were novel, including five missense mutations, three premature stop codons, three frameshift, and one putative splice-site mutation. Based on our results we can conclude there is an absence of hot spot mutations in the MYO7A gene and that this gene plays a major role in Usher syndrome., (2006 Wiley-Liss, Inc.)

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 for mutations in clarin-1 gene among our series of Usher syndrome Spanish patients. Clarin-1 has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II.

Clinical and molecular studies are reported on a Basque family (MRX82) with nonsyndromic X-linked mental retardation (XLMR) in five affected males. A total of 38 microsatellite markers were typed. The XLMR locus has been linked to DXS8067, DXS1001, DXS425, DXS7877, and DXS1183 with a maximum LOD score of 2.4. The haplotype studies and multipoint linkage analysis suggest a localization of the MRX82 locus to an interval of 7.6 Mb defined by markers DXS6805 and DXS7346, in Xq24 and Xq25, respectively. No gene contained in this interval has been so far associated with nonsyndromic mental retardation, except for GRIA3, disrupted by a balanced translocation in a female patient with bipolar affective disorder and mental retardation. However, the search for mutations of this gene did not showed a pathogenic mutation in the present family. Given that there are other eight MRX families overlapping this interval, none of them with known mutation, we conclude that at least one new gene responsible for nonsyndromic mental retardation is located in this region.