Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR.
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ATP-Binding Cassette Transporters↗
Biomedical subjects
C Ayuso
Publications and source records attributed to C Ayuso.
A novel Asp380Ala mutation in the GLC1A/myocilin gene in a family with juvenile onset primary open angle glaucoma.
Glaucoma describes a clinically and genetically heterogeneous group of diseases that result in optic neuropathy and progressive loss of visual fields. A gene for juvenile onset primary open angle glaucoma JOAG) has recently been mapped to 1q21-31. Mutations in the trabecular meshwork induced glucocorticoid response gene (TIGR, also known as myocilin or the GLC1A locus) have been found to cause both juvenile and later onset primary open angle glaucoma. Family TCD-POAG1 is a Spanish kindred, which segregates JOAG in an autosomal dominant fashion. This family was found to be linked to the previously identified GLC1A locus on chromosome 1q. Direct sequencing of the TIGR/myocilin gene showed a heterozygous A to C transition in codon 380, resulting in the substitution of alanine for aspartic acid (Asp380Ala). This substitution created a StyI restriction site, which segregated with the JOAG phenotype and permitted rapid screening of all members of the family. This restriction site was not present in 60 controls.
Adolescent↗
Linkage analysis in Usher syndrome type I (USH1) families from Spain.
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 the USH1B locus shows interesting intrafamilial clinical variability. As regards the remaining six USH1 families, the linkage analysis did not provide conclusive data, although two of them show slight linkage to markers located on chromosome 3q (Zmax=1.880, theta=0.000 for D3S1279), the same location that had previously been assigned to some USH3 families.
Chromosomes, Human, Pair 11↗
First mutation (S340X) in choroideremia gene in a Spanish family. Mutations in brief no. 173. Online.
A study of choroideremia gene was performed in Spanish families affected with this disorder. One abnormal pattern was detected in exon eight corresponding to a new mutation not described before. The mutation was identified as a nonsense mutation S340X.
Choroideremia↗
Identification of two rare variants (G-->A at nucleotide 721; C-->T at nucleotide 5200) in the rhodopsin gene. Mutations in brief no. 187. Online.
The authors report two new rare DNA sequence variants in the Rhodopsin gene. This gene is involved in the pathogenesis of some retinal hereditary disorders as Retinitis Pigmentosa. These rare variants are G-->A at nucleotide 721 of the non-coding region and C-->T at nucleotide 5200 within codon 323 which does not alter the aminoacid cysteine. Therefore, they are not implicated in the development of the Retinitis Pigmentosa disease.
Adenine↗
[Chediak-Higashi syndrome. A laboratory finding].
The Chediak Higashi Syndrome (CHS) is an inherited autosomic recessive immunodeficiency rarely reported. Two pediatric cases are presented, where the first approach to diagnosis was the laboratory report of giant granulation in granulocytes and lymphocytes, observed in peripheral blood smear. In order to confirm the diagnosis of CHS, immunologic tests, skin biopsy, bone marrow aspirate and microscopic hair examination were performed. It is remarked the importance of the careful examination of the blood smear in the detection of this cases, whereas clinic manifestations are not relevant until the hematologic suspicious of the syndrome is evident. The early detection of these patients can lead to bone marrow transplant, which is the only curative treatment to this disorder, lethal in the first decade of life.
Biopsy↗
[A clinical, cytogenetic and molecular study of 10 patients with the Prader-Willi syndrome].
BACKGROUND: The Prader-Willi syndrome (PWS) is a neurogenetic disorder associated with abnormalities in the chromosomal region 15q11-13 of paternal origin. Most cases (65-85%) have a deletion involving the paternally derived chromosome and the remainder (20-25%) have a maternal uniparental disomy. Some patients have a defect in the imprinting process. We report the results of molecular, cytogenetic and clinical studies on 10 PWS patients. PATIENTS AND METHODS: 18 suspected patients were classified as PWS typical or not typical as they fulfilled or not the clinical criteria for PWS. Cytogenic studies-high resolution chromosome banding analyses (HRGTG) and fluorescence in situ hybridization (FISH) -and molecular chromosome genetic analyses--microsatellite markers and Southern blotting--were carried out from peripheral blood lymphocytes. RESULTS: PWS was confirmed in 10 probands. 8 fulfilled the clinical criteria for PWS and showed cytogenetic and/or molecular abnormalities. In 2 patients without clinical or cytogenetic data, diagnosis was confirmed by molecular methods only. Cytogenetic and molecular findings describe a characteristic clinical picture of PWS. CONCLUSIONS: Cytogenetic techniques (FISH and HRGTG) confirmed PWS diagnosis in 40% of cases, microsatellite studies in 70% of them and Southern blotting (the metilation test) in 100% cases. Southern blotting is the method of choice for rapid diagnostic testing of patients suspected of having PWS.
Adolescent↗
A new locus for autosomal recessive retinitis pigmentosa (RP19) maps to 1p13-1p21.
Autosomal recessive retinitis pigmentosa (arRP) is characterized by considerable allelic and nonallelic heterogeneity. Mutations have been described in the rhodopsin gene (RHO), the genes encoding the alpha and beta subunits of rod phosphodiesterase (PDEA and PDEB), and the gene encoding the alpha subunit of the cGMP-gated channel (CNCG). In addition, linkage studies in single extended pedigrees have defined two new arRP loci, at 1q and 6p. To identify the disease gene in a Spanish consanguineous arRP family, a linkage analysis was undertaken. After testing 102 polymorphic markers, a significant positive lod score (Zmax = 3.64 at theta = 0) was obtained with marker D1S188 at 1p13-p21, the same region where the Stargardt and fundus flavimaculatus (FFM) loci were previously defined. Exhaustive ophthalmologic examination of the patients clearly distinguished the disease from the Stargardt and FFM phenotypes and revealed an atypical form of arRP with choroidal atrophy as a distinctive feature.
Aged↗
67Ga scintigraphy for the evaluation of recurrences and residual masses in patients with lymphoma.
67Ga scintigraphy has proven to be of value in the evaluation of patients with lymphoma, especially in their management after treatment. In this study, computed tomography (CT) and 67Ga scans were compared in 53 patients with lymphoma who had previously been treated. Twenty-eight were patients in continuous clinical remission in whom recurrence was suspected. The remaining 25 patients were studied between 1 and 3 months post-treatment to assess a residual mass. The sensitivity for the detection of lymphoma recurrence was 88% for 67Ga, with two false-negative results, and 59% for CT, with seven false-negative results. In the diagnosis of recurrence, the specificity of 67Ga was 100% and that of CT 72%, with three false-positive results. Therapeutic response was assessed in 25 patients and the ability to predict response to treatment resulted in a specificity of 86% for 67Ga and 81% for CT. Treatment failed in four patients, as detected by 67Ga scan, whereas CT did not detect any of these. In the remaining 21 patients who showed good response to treatment, there were three false-positive results for 67Ga and four for CT. 67Ga scintigraphy can detect relapse more accurately and much earlier than CT, as well as diagnose complete remission after treatment. Therefore, 67Ga scintigraphy should be used routinely in monitoring response to treatment in lymphoma.
Abdomen↗
A novel mutation in the BRCA1 gene in a German early-onset breast cancer family.
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Adult↗
Novel rhodopsin mutation in an autosomal dominant retinitis pigmentosa family: phenotypic variation in both heterozygote and homozygote Val137Met mutant patients.
A family affected with autosomal dominant retinitis pigmentosa (RP) is presented. Two clinically affected patients (mother and daughter) were heterozygous for the same novel missense mutation (Val137Met) of the rhodopsin gene (RHO). Both heterozygous and homozygous cases were observed among their few symptomatic relatives. Wide clinical variation was exhibited among the individuals with mutations in this family. None of the controls showed this change in RHO, nor has it been previously reported in other RP families. No other RHO mutation was observed. Additional genetic or environmental factors could play a role in modulating the penetrance and clinical expression of this RHO mutation.
Base Sequence↗
Autosomal recessive retinitis pigmentosa in Spain: evaluation of four genes and two loci involved in the disease.
Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous form of retinal degeneration. The genes for the beta-subunit of rod phosphodiesterase (PDEB), rhodopsin (RHO), peripherin/RDS (RDS) and the rod outer segment membrane protein 1 (ROM1), as well as loci at 6p and 1q, have previously been reported as the cause of ARRP. In order to determine whether they are responsible for the disease in Spanish pedigrees, linkage and homozygosity studies using markers at these loci were carried out on 47 Spanish ARRP families. SSCP analysis was performed to search for mutations in the genes cosegregating with the disease in particular pedigrees. Three homozygous mutations in the PDEB gene were found, thus accounting for 6% of the cases. No other disease-causing mutation was observed in the other genes analysed, nor was significant evidence found for the involvement of the loci at 6p or 1q. On the basis of these data, it is unlikely that these genes and loci account for a considerable proportion of ARRP cases.
Calcium-Binding Proteins↗
G106R rhodopsin mutation is also present in Spanish ADRP patients.
A large family affected with autosomal dominant retinitis pigmentosa (ADRP) with a sectorial phenotype showed a previously described (G to A) mutation in the rhodopsin gene resulting in the substitution of a glycine residue by an arginine in codon 106 of rhodopsin. This mutation shows some unusual characteristics, such as initial pathology of the inferior retina, superior visual field with normal disc and retinal vessels, and ERG findings that show a modest reduction in both cone and rod amplitudes with normal implicit times. The Gly 106 Arg mutation has been previously reported in American and British patients. Its presence in a Spanish ADRP family confirms that it and its homogeneous associated phenotype are geographically widespread.
Adolescent↗
Homozygous tandem duplication within the gene encoding the beta-subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa.
Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the rhodopsin and phosphodiesterase beta-subunit (PDEB) loci have been reported. To assess the involvement of PDEB in ARRP families from Spain, we screened a panel of 19 families for linkage to markers within or close to the PDEB gene. Homozygosity was also tested in cases of consanguinity. This combined approach ruled out PDEB as the cause of the disease in all but one of the families. Molecular characterization of the gene in that family (a consanguineous pedigree) revealed a homozygous 71-bp tandem duplication in exon 1 of the affected member, the parents being heterozygous. This defect causes a frameshift mutation which leads to a premature stop codon, suggesting that this mutant allele is the underlying cause of ARRP in this patient. According to the data presented here, the PDEB gene is not the main gene responsible for ARRP, but accounts for about 5% of the cases.
Base Sequence↗
Somatic stability in chorionic villi samples and other Huntington fetal tissues.
We have studied different tissues from two affected fetuses with Huntington's disease (HD). In the first case the analysis was performed at 11 weeks of pregnancy; CAG repeats from seven different tissues were compared with the results obtained in the chorionic villi sample (CVS). We found 42 CAG repeats in all samples. In the second case the study was done at 12 weeks; eight tissues (including brain) were studied and compared with the CVS; in all of them, 44 CAG repeats were obtained. Our results show a somatic stability in the different analyzed tissues and suggest that mitotic instability can be a secondary consequence of neuronal degeneration and gliosis. Likewise, our data show great viability in the prenatal diagnosis (PD) of Huntington's disease using samples from any tissue.
Abortion, Therapeutic↗
Evidence against involvement of recoverin in autosomal recessive retinitis pigmentosa in 42 Spanish families.
Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the genes encoding rhodopsin, the beta subunit of rod phosphodiesterase (PDEB) and, recently, in the gene for rod cGMP-gated channel, have been reported. However, detailed genetic involvement has not been ascertained in the great majority of cases. Recoverin, another member of the light transduction pathway, is a candidate gene for ARRP. We report the first analyses of the involvement of the recoverin gene (RCV1) in 42 Spanish ARRP families. Linkage and homozygosity studies with an intragenic polymorphism and the close markers D17S945 and D17S786 ruled out RCV1 as the cause of ARRP in 38 pedigrees. In the four remaining families, single strand conformation polymorphism analysis of the recoverin-coding region detected no mutations in the parents or in the affected members. These results strongly suggest that mutations in the RCV1 gene are not responsible for ARRP in these families.
Base Sequence↗
Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients.
BACKGROUND & AIMS: The progression of hepatocellular carcinoma may be influenced by estrogens. This has offered the rationale for evaluating the therapeutic usefulness of estrogen-receptor blockers; it is being debated whether long-term tamoxifen administration improves survival in patients with this neoplasm. The aim of this study was to assess the efficacy of tamoxifen administration in the treatment of hepatocellular carcinoma. METHODS: One hundred twenty patients with this neoplasm who were not suitable for surgery, ethanol injection, or transarterial embolization were included in a placebo-controlled trial and randomized to tamoxifen, 20 mg/day per os, (group A, n = 58) or placebo (group B, n = 62). Patients with terminal diseases were excluded. RESULTS: Both groups were similar with regard to sex, age, liver function (Child-Pugh's score, 6.5 +/- 1.4 vs. 6.4 +/- 1.4), baseline performance status, and tumor stage. Tamoxifen had no antitumoral effect with no differences in the survival between groups (1- and 2-year actuarial rate: group A, 51% and 27%; and group B, 43% and 29%; P = 0.75), even when stratifying patients according to baseline status. Furthermore, there were no differences in the probability of disease progression (P = 0.46) and baseline performance status maintenance (P = 0.93) during follow-up. CONCLUSIONS: Tamoxifen has no efficacy in the treatment of patients with advanced hepatocellular carcinoma.
Aged↗
Transarterial embolization for hepatocellular carcinoma. Antibiotic prophylaxis and clinical meaning of postembolization fever.
BACKGROUND/AIMS: The aim of this prospective randomized controlled trial was to investigate the need for prophylactic antibiotherapy in patients with cirrhosis and hepatocellular carcinoma who underwent transarterial embolization and to establish the parameters that determine the development of fever > 38 degrees C after this procedure. METHODS: Sixty-one consecutive patients with cirrhosis undergoing 75 procedures were randomized into Group I [(n = 37) allocated to receive prophylactic antibiotics (Cefotaxime + Metronidazole)] and Group II [(n = 38) allocated to receive no antibiotic treatment]. RESULTS: Twelve of the 37 patients (32%) in Group I and 13 of the 38 patients (34%) in Group II developed fever > 38 degrees C after treatment. However, none of them developed bacterial infection, and all biological fluid cultures were negative. A logistic regression analysis disclosed that the obtention of an extensive tumor necrosis was the unique parameter independently associated with the development of fever. CONCLUSIONS: Antibiotic prophylaxis is therefore not necessary in patients with cirrhosis and hepatocellular carcinoma undergoing transarterial embolization. The appearance of fever after this procedure does not indicate bacterial infection; it rather represents a clinical marker of extensive tumor necrosis and thus of a favorable response to treatment.
Aged↗