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Biomedical subjects

G Antiñolo

Publications and source records attributed to G Antiñolo.

At least 19 recordsLinked to original sources
PubMed2006

A novel genetic study of Chinese families with autosomal recessive retinitis pigmentosa.

Autosomal recessive retinitis pigmentosa (arRP) is the commonest form of RP worldwide. To date 22 loci have been implicated in the pathogenesis of this disease; however none of these loci independently account for a significant proportion of recessive RP. Linkage studies of arRP in consanguineous families have been mainly based on homozygosity mapping, but this strategy cannot be applied in the case of non-consanguineous families. Therefore, we implemented a systematic approach for identifying the disease locus in three non-consanguineous Chinese families with arRP. Initially, linkage analysis using SNPs/microsatellite markers or mutation screening of known arRP genes excluded all loci/genes except RP25 on chromosome 6. Subsequently a whole genome scan for the three families using the 10K GeneChip Mapping Array was performed, in order to identify the possible disease locus. To the best of our knowledge this is the first report on the utilisation of the 10K GeneChip to study linkage in non-consanguineous Chinese arRP. This analysis indicates that the studied families are probably linked to the RP25 locus, a well defined arRP locus in other populations. The identification of another ethnic group linked to RP25 is highly suggestive that this represents a major locus for arRP.

Asian People↗
PubMed2006

Mutation profile of the MYO7A gene in Spanish patients with Usher syndrome type I.

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.

DNA Mutational Analysis↗
PubMed2006

Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II.

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.

Adolescent↗
PubMed2005

The -670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis C.

Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C virus (HCV) infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas. Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, -1377G > A and -670A > G. We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C. A cohort of 197 patients with chronic hepatitis C and 100 controls were analysed for both polymorphisms by Fluorescence Resonance Energy Transfer using specific probes and the Lightcycler system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system. We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection. However, we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the -670A > G variant among those patients with higher Knodell's scores (P = 0.049) and necroinflammatory activity (P = 0.036). The -670A allele was associated with higher levels of periportal necrosis (P = 0.012). In conclusion, our findings suggest an association between the -670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C.

Adolescent↗
PubMed2005

Ancestral RET haplotype associated with Hirschsprung's disease shows linkage disequilibrium breakpoint at -1249.

BACKGROUND: Hirschsprung disease (HSCR) is a complex disorder with traditional germline mutations in RET in up to 30% of familial cases and in 3% of sporadic cases in a population-based series. We have previously demonstrated that an ancestral haplotype at the 5' end of RET (haplotype 0) was strongly associated with a large subset of isolated HSCR cases and that a putative low penetrance susceptibility locus was encompassed within this ancestral haplotype, anchored by exon 2 SNP A45A. OBJECTIVE: To determine the 5' extent of the HSCR-associated ancestral haplotype by defining the linkage disequilibrium breakpoint in search for the low penetrance susceptibility locus. METHODS: Systematic screening of the region upstream of the anchoring A45A SNP, comprising RET intron 1, exon 1, and promoter in 117 population-based HSCR cases and 100 controls. Dual luciferase assay to determine differential activities between SNP combinations near a transcription start site. RESULTS: New SNP's were found which formed upstream haplotypes, anchored by A45A, in linkage disequilibrium with HSCR (2 = 76.96, p<0.00000001). Linkage disequilibrium appeared to break at the -1249C/T SNP. Further, the HSCR-associated genotype (00) was found in >60% of HSCR but only 2% of controls. Because only 2 variants, -200A>G and -196C>A, lie within the promoter region and are in proximity to the transcriptional start site (at -195), we modelled these combinations into constructs for luciferase reporter assay. The HSCR-associated SNP combination showed the lowest activity and the control-associated combination, the highest. CONCLUSIONS: Our observations seem to discard the existence of a HSCR-causing mutation as it is conceived in the traditional sense, but strengthen the idea of a specific combination of variants conferring susceptibility to the disease in a low penetrance fashion. The data derived from our functional "in vitro" studies would suggest that the HSCR-associated haplotype 0 may result in a lower level of expression of the RET gene [corrected]

Case-Control Studies↗
PubMed2005

Spanish family with myalgia and cramps syndrome.

A Spanish family is reported with dystrophinopathy of myalgia and cramps syndrome type. There were five affected males and three females, and also six asymptomatic carriers. Muscle biopsy showed a dystrophic pattern, but immunohistochemistry carried out with three anti-dystrophin antibodies was normal. Dystrophin analysis by western blot revealed a dystrophin of reduced quantity and molecular weight. DNA analysis showed a deletion of the dystrophin gene involving exons 45-52. The natural history of this disorder and the large intrafamilial clinical variability are discussed.

Adolescent↗
PubMed2005

Polymorphisms in the promoter regions of FAS and FASL genes as candidate genetic factors conferring susceptibility to endometriosis.

Although the pathophysiological mechanisms leading to endometriosis remain unknown, several hypothesis have been proposed, including a dysregulation of the normal apoptotic process which takes place in the endometrium. One of the apoptotic pathways playing a crucial role in the programmed cell death within the endometrium is the Fas-FasL system. In this study we have performed a case-control analysis in order to evaluate three polymorphisms located within FAS (-1377G>A and -670A>G) and FASL (-843C>T) genes, as susceptibility factors for endometriosis. We have analysed a series of women with endometriosis compared respectively to a group of women without symptoms of the disease, and to a group of confirmed unaffected women. The genotyping of the three variants was carried out by Fluorescence Resonance Energy Transfer (FRET) technology, and statistical analysis was performed using chi2 test with Yates correction. Our results show that the differences in the distribution of the polymorphic variants were not statistically significant when the group of patients was compared to the other groups. Thus, it seems to indicate that the variants here analysed are not involved in the pathogenesis of the disease in our population. However this does not let us to completely exclude such genes as potential candidates for the disease. A complete genetic analysis of the genes involved in the intricate regulatory system of the apoptosis may lead to the identification of susceptibility factors for the disease and a better understanding of its etiology.

Adult↗
PubMed2004

Analysis of the involvement of CCR5-Delta32 and CCR2-V64I variants in the development of endometriosis.

Several arguments support the proposal that the cytokine network plays a critical role in the aetiology of endometriosis. Among various chemokines, regulated-on-activation, normal-T-cell-expressed and -secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) concentrations have been shown to be increased in the peritoneal fluid of women with endometriosis. Some studies have demonstrated that, in the context of endometriosis, these chemokines are involved in apoptosis, angiogenesis and/or chemotaxis. Since the chemokines exert their effects by binding to their receptors, it would be plausible that factors affecting such interactions might play a role in the pathogenesis of endometriosis. Thus we postulated that the genes encoding CCR5 and CCR2, which are the receptors for RANTES and MCP-1 respectively, could be good candidate genes for the disease. We have used real-time PCR and FRET technologies to genotype and evaluate the variants CCR5-Delta32 and CCR2-V64I, as susceptibility factors in a cohort of Spanish women with endometriosis. No differences have been found in the frequencies of the two polymorphisms nor in the haplotype/genotype distribution between cases and controls. These data would suggest the lack of association between these polymorphisms and endometriosis in our population, although they do not permit us to discard completely a possible role of other variants within CCR5 and CCR2 genes in this pathology.

Endometriosis↗
PubMed2004

Analysis of CCR5-Delta 32 and CCR2-V64I polymorphisms in a cohort of Spanish HCV patients using real-time polymerase chain reaction and fluorescence resonance energy transfer technologies.

Nowadays it is clear that chemokine-chemokine receptor interactions are important in chronic hepatitis C virus (HCV) infection. The objective of the present study was to elucidate the involvement of the CCR5-Delta 32 and CCR2-V64I polymorphisms in the response to the HCV infection, as well as in the histological damage and the outcome of the infection. A cohort of 139 patients with hepatitis C and 100 healthy blood donors were analysed for both polymorphisms using real-time polymerase chain reaction (PCR) and LightCycler technology. We have detected the CCR5-Delta 32 allele in 15 of 278 HCV chromosomes (5.4%) and 15 of 200 control chromosomes (7.5%). The CCR2-V64I allele was present in 24 of 278 HCV chromosomes (8.6%) and 19 of 200 control chromosomes (9.5%). Analysis of the histological parameters showed no statistical significance when comparing the patients carrying the variants vs the cases with the wild-type allele. Our results seem to indicate that the CCR5-Delta 32 and CCR2-V64I polymorphisms are not related to the response to HCV infection, histological damage and outcome of infection in our cohort of Spanish HCV patients.

Biopsy↗
PubMed2003

Evaluation of germline sequence variants within the promoter region of RANTES gene in a cohort of women with endometriosis from Spain.

The RANTES (regulated upon activation normal T cells expressed and secreted) chemokine, is known to be expressed in endometriotic lesions in a concentration correlating with the severity of endometriosis. Since it has been widely demonstrated that endometriosis has a genetic basis, we postulated that the gene encoding RANTES could be a good candidate gene for the disease. We have used fluorescence resonance energy transfer (FRET) technology to genotype and evaluate the role of the variants -403G-->A and -28C-->G, located within the promoter region of the gene, as susceptibility factors in a cohort of Spanish women with endometriosis. No differences have been found in the allelic frequencies of both variants nor in the haplotype/ genotype distribution between patients and controls. These data are consistent with the lack of association between these polymorphisms and endometriosis in our population. They do not exclude completely a possible role of other variants within RANTES gene in this pathology.

Adult↗
PubMed2001

[Molecular analysis of the RPE65 gene in 72 Spanish families with autosomal recessive retinitis pigmentosa].

BACKGROUND: Autosomal recessive retinitis pigmentosa (arRP) is the most common form of retinitis pigmentosa (RP). It is characterized by a high degree of allelic and non-allelic genetic heterogeneity. Previously,it has been demonstrated that the RPE65 gene is responsible for 2% recessive or isolated RP cases and 16% Leber's congenite amaurosis cases. Although the concrete function of RPE65 is unknown as yet, it has been found to be involved in vitamin A metabolism and rhodopsin regeneration. PATIENTS AND METHOD: We studied the involvement of the RPE65 gene in 72 arRP Spanish families by means of indirect molecular and mutation analysis. RESULTS: The results obtained using the intragenic microsatellite marker D1S2803 allowed us to exclude RPE65 as the causative gene of the disease in 80.5% of the families studied. Three new variants of the RPE65 gene have been identified: IVS6-43delA, IVS6-42delT and IVS6-33CG. We found that IVS6-33C-->G was a common polymorphism. The other variants, namely IVS6-43delA and IVS6-42delT, were not identified in 150 control chromosomes studied. The segregation analysis of IVS6-42delT variant seemed to exclude it as being involved in the disease. CONCLUSIONS: Our results argue against the involvement of RPE65 gene in the families studied, indicating that the prevalence of RPE65 abnormalities in arRP Spanish families may be lower than that observed in other populations.

Carrier Proteins↗
PubMed2001

Fluorescence resonance energy transfer analysis of CCR-V64I and SDF1-3'a polymorphisms: prevalence in southern Spain hiv type 1+ cohort and noninfected population.

The relationship between host genotype and AIDS, as well as the different genotype frequencies observed in different populations, have become important topics in HIV research. Therefore, the development of methods that provide faster and reliable results may contribute to further development and knowledge of those topics. We present the results of genotyping SDF1-3'A and CCR2-V64I in 440 HIV-1-infected people and 100 noninfected controls from southern Spain, using a novel method based on real-time PCR with LightCycler technology and fluorescence resonance energy transfer. Frequencies obtained were 23.8% for SDF1-3'A and 9.5% for CCR2-V64I for both HIV+ cohort and general population. Both polymorphisms are in accordance with the Hardy-Weinberg equilibrium law and no differences between patients and controls have been observed.

Alleles↗
PubMed2001

Mutations P51U and G122E in retinal transcription factor NRL associated with autosomal dominant and sporadic retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most frequent form of inherited retinopathy. RP is genetically heterogeneous with autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) accounts for about 20-25% of all RP cases. At least ten adRP loci have so far been mapped. However, mutations causing adRP have been identified only in four retina-specific genes: RHO (encoding rhodopsin) in approximately 20% of adRP families, peripherin/RDS (3-5% of adRP) and recently RP1 (Pierce et al., 1999, Sulivan et al., 1999) and NRL gene. Only one mutation in the NRL gene causing adRP has so far been reported (Bessant et al., 1999). Here we report a novel mutation Pro51Leu in an adRP Spanish family supporting that mutation in NRL is the cause of adRP. A second missense mutation Gly122Glu has been observed in a simplex RP patient that may represent a sporadic case of retinitis pigmentosa. Hum Mutat 17:520, 2001.

Base Sequence↗