Oxidative stress-related clastogenic factors in plasma from Chernobyl liquidators: protective effects of antioxidant plant phenols, vitamins and oligoelements.
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Adult↗
Biomedical subjects
J Feingold
Publications and source records attributed to J Feingold.
Lack of association between juvenile myoclonic epilepsy and GABRA5 and GABRB3 genes.
Alpha 5 and beta 3 GABAA receptor genes are major candidates for epilepsy, as they code for subunits of the most important human inhibitory neurotransmitter. Moreover, they are located within a region of the human genome previously implicated in disorders including epilepsy. We carried out an association study between dinucleotide repeat polymorphisms in these two genes and juvenile myoclonic epilepsy (JME). JME is the most common idiopathic epilepsy and is characterized by a complex mode of inheritance. We did not find significant differences between controls and patients for allele or genotype frequencies.
Adult↗
Serotonin transporter gene and manic depressive illness: an association study.
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Adult↗
The influence of the angiotensin I converting enzyme genotype in familial hypertrophic cardiomyopathy varies with the disease gene mutation.
Familial hypertrophic cardiomyopathy is an autosomal dominant genetically heterogeneous disease characterized by a partial penetrance and variable expressivity. Previous studies showed that the extent of hypertrophy is influenced by the angiotensin I converting enzyme insertion/deletion (I/D) polymorphism. Recently, molecular genetic analysis revealed the existence of healthy carriers and that as many as a quarter of genetically affected individuals do not express the disease. This data prompted us to re-investigate the role of the angiotensin I converting enzyme polymorphism on hypertrophy by assessing both clinically affected individuals and healthy carriers. For this, several families with mutations in the cardiac myosin binding protein C or the beta-myosin heavy chain genes were analysed. The mean maximal intraventricular septum thickness was compared as a function of angiotensin I converting enzyme genotypes in all genetically affected individuals (n = 114), and in subsets of subjects carrying either a splice acceptor site mutation in the cardiac myosin binding protein C gene (n = 33), or various missense mutations in the cardiac beta-myosin heavy chain gene (n = 81) or finally, mutation in the Arg403 codon of the beta-myosin heavy chain gene (n = 54). Significant association between the D allele and hypertrophy was observed only in the case of Arg403 codon mutations (mean septum thickness for subjects with the DD genotype: 19.3 +/- 2.7 mm: with the ID genotype: 13.4 +/- 1.3 mm and with the II genotype: 11.0 +/- 0.9 mm; P < 0.02). These results were confirmed by the chi 2 test showing an over-representation of DD genotype in patients carrying an Arg403 codon mutation associated with septal hypertrophy (P < 0.05). Our data confirms that the angiotensin I converting enzyme genotypes can influence the phenotypic expression of hypertrophy and shows that this influence depends on the mutation, raising the concept of multiple genetic modifiers in familial hypertrophic cardiomyopathy.
Adult↗
Manic depressive illness and tyrosine hydroxylase gene: linkage heterogeneity and association.
Several studies have implicated the tyrosine hydroxylase (TH) locus within the 11p15 region in susceptibility to manic depressive illness (MDI). This possibility was further investigated by both parametric (lod score) and nonparametric (affected-pedigree-member and a case-control study) methods of analysis in 11 French MDI families and in a sample of 200 unrelated subjects. Both types of analyses corroborate the implication of this locus, and positive lod scores were obtained in two families, which most likely reflects genetic heterogeneity. Statistical analyses were also performed including available data from published reports. These analyses, which allowed for genetic heterogeneity, substantiated our findings. The combined maximum lod score for all the families studied was 3.68 at theta = 0.00 (number of families: 36) assuming heterogeneity (alpha = 15%, P = 0.01). Taken together these results converge to suggest that the risk factors for MDI lie in the 11p15 region with TH being the most likely candidate gene.
Alleles↗
Asthma, nasal allergies, and multiple sclerosis.
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Adult↗
Further epidemiological evidence for anticipation in schizophrenia.
Anticipation describes an inheritance pattern within a pedigree in which disease severity increases, and/or age at onset decreases, in successive generations. This phenomenon has been described in different samples of schizophrenic subjects, and could explain many inconsistencies in the inheritability of schizophrenia. Anticipation is, however, subject to numerous and significant biases, partially controlled by different methodologies used in different studies. We analyzed the anticipation effect on an original sample of schizophrenic patients (n = 57) who had at least one other schizophrenic in their family belonging to another generation (father/mother, uncle/aunt, son/daughter). We tested the anticipation effect according to previously published methodologies, such as percentages of parent-child pairs showing negative versus positive anticipation, comparison of anticipation limited to parent-child or uncle-nephew pairs, anticipation analysis on the basis of families with unilineal origins only, and comparison of the age at onset-survival distribution of the two generations. The 31 schizophrenic subjects who belonged to the younger generation had a significantly earlier age at onset (24.58 years) than the 26 schizophrenic subjects who belonged to the older generation (36.46 years). Whatever the method used to control biases, we significantly found earlier age at onset for schizophrenic patients from the younger generation. There is strong evidence for the existence of the anticipation effect in schizophrenia in our sample, as well as in various others, which may elucidate numerous inconsistencies in clinical and epidemiological data which characterize schizophrenia. Looking for expanded trinucleotide repeats is thus the next step to detect the gene(s) that are potentially involved.
Adult↗
Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma following autologous stem cell transplantation.
Bacterial meningitis is an unusual complication of bone marrow transplantation. We report a case of Stomatococcus mucilaginosus meningitis in a patient with multiple myeloma shortly after an autologous peripheral blood stem cell transplant. The infection resolved with a combination of intravenous penicillin G and chloramphenicol, and intrathecal vancomycin.
Bone Marrow Transplantation↗
Epidemiological study of the genetics and environment of asthma, bronchial hyperresponsiveness, and atopy: phenotype issues.
The Epidemiological Study of the Genetics and Environment of Asthma (EGEA) combined a case-control study and a family study. The total sample of 1,854 consisted of 348 patients with asthma selected through chest clinics and 416 control subjects and nuclear families ascertained through the cases. The protocol included standardized questionnaires, bronchial responsiveness, allergen skin-prick tests according to international protocols, total serum immunoglobulin E (IgE) level measurements, and blood eosinophilia. Criteria used to select subjects with asthma and determine asthma status of relatives for affected sibling pair linkage analysis are described. Based on figures from the 348 asthma cases of the EGEA study, issues relative to the definition of severe asthma and intermediate phenotypes such as bronchial responsiveness and allergic markers are discussed. Given the phenotypic heterogeneity involved, relevant phenotypes that may lead to the detection of genetic factors will depend on the hypothesis tested. Standardization of primary data and subphenotypes is a prerequisite for pooling data, which will be needed in the future to better understand the genetics and environmental factors of asthma.
Adolescent↗
Penetrance of familial hypertrophic cardiomyopathy.
Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant cardiac disease for which the penetrance remains a much-debated issue. Since the recent identification of the genes involved in the disease, the penetrance of FHC has not been reassessed in a large genotyped population. The aim of our study was therefore to evaluate it, according to age and sex, in ten families with previously identified mutations. Among 178 individuals we studied, 90 were genetically affected (9 different mutations in 3 genes). We found that penetrance, assessed by classical echocardiographic and electrocardiographic criteria, was (1) incomplete: 69%; (2) age-related: 55% between 10 and 29 years old, 75% between 30 and 49 y. and 95% over 50 y.; (3) greater in males than in females: 77% vs 58%, age-adjusted odds ratio: 3.98, CI 95%: 1.34 to 11,48; (4) similar for the genes analyzed. The consequences of these results for genetic counseling and linkage analyses are discussed.
Adolescent↗
[Presymptomatic diagnosis in genetics: the model of Huntington disease].
Huntington's disease represents the most typical disorder concerning presymptomatic testing of late onset hereditary disorders. Predictive testing involves several ethical problems especially related to the severity of the disease and its absence of treatment. Other genetic disorders for instance hereditary breast cancer rise the same problems.
Ethics, Medical↗
Linkage disequilibrium and extended haplotypes in the HLA-A to D6S105 region: implications for mapping the hemochromatosis gene (HFE).
The hemochromatosis gene (HFE) maps to 6p21.3, in close linkage with the HLA Class I genes. Linkage disequilibrium (LD) studies were designed to narrow down the most likely candidate region for HFE, as an alternative to traditional linkage analysis. However, both the HLA-A and D6S105 subregions, which are situated 2-3 cM and approximately 3 Mb apart, have been suggested to contain HFE. The present report extends our previous study based upon the analysis of a large number of HFE and normal chromosomes from 66 families of Breton ancestry. In addition to the previously used RFLP markers spanning the 400-kb surrounding HLA-A, we examined three microsatellites: D6S510, HLA-F, and D6S105. Our combined data not only confirm a peak of LD at D6S105, but also reveal a complex pattern of LD over the i82 to D6S105 interval. Within our ethnically well-defined population of Brittany, the association of HFE with D6S105 is as great as that with HLA-A, while the internal markers display a lower LD. Fine haplotype analysis enabled us to identify two categories of haplotypes segregating with HFE. In contrast to the vast majority of normal haplotypes, 50% of HFE haplotypes are completely conserved over the HLA-A to D6S105 interval. These haplotypes could have been conserved through recombination suppression, selective forces and/or other evolutionary factors. This particular haplotypic configuration might account for the apparent inconsistencies between genetic linkage and LD data, and additionally greatly complicates positional cloning of HFE through disequilibrium mapping.
Base Sequence↗
[Sickle cell anemia: study of the pediatric mortality in Ile de France from 1985 to 1992].
BACKGROUND: Sickle cell anemia is now relatively frequent in France. Its clinical course is punctuated by acute episodes that threaten the life, specially during the first year of life. POPULATION AND METHODS: The files of 26 children (14 boys, 12 girls) dead from sickle cell disease between 1985 and 1992 were retrospectively studied. These files concerned patients from the Ile-de-France area. RESULTS: Their mean age at time of diagnosis was 13.7 months (0 to 3 years 4 months); mean age was 5.5 years at time of death. Infection was the cause of death in 15 patients (S pneumoniae in eight patients despite prophylactic penicillin and pneumococcal vaccine in the majority of them). Splenic sequestration crisis was the cause of death in three patients less than 5 years of age; vasocclusive crisis resulting in cerebral infarction was the cause in three patients aged 7.5 to 13 years. Mortality calculated from those patients followed since 1987 (total: 2,063 years) was 0.29% person/year. CONCLUSION: Comfort of patients and risk of permanent disability become the main factors of choice for new treatments such as chemotherapy or bone marrow transplantation.
Adolescent↗
No evidence for genomic imprinting in liver-born Down syndrome patients.
Despite numerous studies, the clinical heterogeneity of Down syndrome has no explanation. We have attempted to investigate the role of genomic imprinting in the phenotype of liveborn Down syndrome patients. Hundred fifty eight patients were investigated for parental origin of the extra chromosome 21 with standard cytogenetic analyses and with DNA plymorphic markers. The extra chromosome 21 was of paternal origin in 8 cases and of maternal origin in 150 cases. The phenotype of Down syndrome patients in whom the nondisjunction was of maternal origin, was not different from the phenotype of Down syndrome patients in whom the nondisjunction was of paternal origin. We conclude that imprinting may probably not play a role in the heterogeneity of Down syndrome phenotype.
Adolescent↗
Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33.
Three hundred million individuals are at risk of infection by schistosomes and around 200,000 die each year of this disease. Severe clinical disease in schistosomiasis is often the consequence of heavy infection which, in several endemic areas, are determined largely by the susceptibility/resistance of individuals. Previously, we reported evidence, based on a segregation analysis in Brazilian pedigrees, that intensity of infection by Schistosoma mansoni was influenced by a major gene, indicating that host genetic factors are probably critical in controlling schistosome infection and disease development. To localize this gene, referred to as SM1, we performed a genome-wide study on 142 Brazilian subjects belonging to 11 informative families Our results show a linkage to only one region, on chromosome 5q31-q33, with maximum two-point lod scores of +4.74 and +4.52 for D5S636 and the colony stimulating factor-1 receptor marker (CSF1R), respectively. This was corroborated by multipoint analysis, indicating a close proximity to CSF1R as the most likely location of SM1. This region contains several candidate genes encoding immunological molecules that were shown to play important roles in human protection against schistosomes.
Brazil↗
Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island.
A series of patients affected by a muscular dystrophy, similar to the original description of a juvenile scapulo-humeral form by Erb in 1884 and fitting with the criteria used to define limb-girdle muscular dystrophies, was discovered in a small community living in the southern part of Reunion Island in the Indian Ocean. A detailed clinical analysis was conducted over 5 years on a cohort of 20 patients. This community presented a high degree of consanguinity as it was segregated from the majority of the island population for more than a century. In previous molecular genetic studies, the disease locus has been mapped to chromosome 15p. Mutations were recently identified in a gene located in this region encoding for muscle-specific calcium activated neutral protease (CANP3). Clinical, pathological, genetic and complete identification of the mutations are presented here, establishing, for the first time, precise clinico-genetic correlations in this form of autosomal recessive, juvenile, limb-girdle muscular dystrophy (LGMD).
Adolescent↗
Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians.
Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.
Adult↗
A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities.
An unusual familial case of three sibs with a partial duplication of distal Xp sequences is described. The proband, an 18 year old boy, showed mental retardation, severe dysmorphic features, hypogonadotrophic hypogonadism (HHG), and hypoplastic external genitalia. His karyotype was 46,Y,inv dup(X) (p22.11-->p 22.32). The proband has two sisters each with the same inv dup(Xp) chromosome. Both sisters presented with short stature but were otherwise phenotypically normal. The abnormal X chromosome was inactive in the majority of cells examined. Southern blot dosage analysis indicated a duplication of distal Xp sequences. The proximal breakpoint is located between DXS28 and DXS41, and is therefore at least 2 Mb distal to the DSS locus. The relationship between the phenotype and the Xp duplication is discussed.
Abnormalities, Multiple↗