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J Feingold

Publications and source records attributed to J Feingold.

At least 109 records · Page 6Linked to original sources
PubMed1996

Anticipation in schizophrenia: new light on a controversial problem.

OBJECTIVE: Anticipation, recently found in several neuropsychiatric disorders, is an inheritance pattern within a pedigree in which disease severity increases or age at onset decreases in successive generations. Demonstration of genetic anticipation in schizophrenia could be of heuristic value, since unstable trinucleotide repeat DNA is known to be the biological basis of anticipation. However, to overcome one of the major ascertainment biases that might mimic anticipation--namely, the fact that patients in different generations are not interviewed at the same age, resulting in a greater chance of finding a later age at onset in the older generation--a new method of investigating anticipation was used. METHOD: The study subjects were 97 systematically ascertained schizophrenic patients belonging to 24 families with at least two generations affected who were identified during a 1-year prevalence study in a limited geographical area of Reunion Island (Indian Ocean). A method of calculating expected age at onset according to age at interview was used in the analyses. RESULTS: In the younger generation of patients, the observed age at onset (21.80 years) was earlier than the expected age at onset (24.95 years), demonstrating anticipation, even when five additional biases that can mimic this genetic effect--the proband effect, the presence of an affected father or mother, the bilineality of the illness, the fertility effect, and the cohort effect--were taken into account. CONCLUSIONS: Evidence for anticipation was demonstrated in this group of schizophrenic patients. This may help the search for pathological genes implicated in the genesis of schizophrenia.

Adult↗
PubMed1996

Implications of prenatal diagnosis of sickle cell disease.

Prenatal diagnosis (PND) of sickle cell disease (SCD) has been feasible since about 15 years. The number of PND performed for SCD has constantly increased during these years, but its availability raises difficult ethical questions for parents and counsellors. Concerning at-risk parents, only 50% (data in the literature) to 70% (personal data) ask for PND. Our study shows that mainly cultural reasons, then religious ones, educational level and the number of children in the family weigh on the parents' decision to request this diagnosis. The counsellors' position is difficult since clinical severity of the disease is highly variable, there is no early prognostic factor, and the median life expectancy of patients in industrialized countries exceeds 40 years. We need to define a counselling which would consider the image of the illness in the populations involved, in order to help parents understand the implications of the choice they are asked to make.

Abortion, Eugenic↗
PubMed1995

Lack of association between alcohol-dependence and D3 dopamine receptor gene in three independent samples.

Numerous studies on the involvement of dopamine receptors in the genetics of alcoholism focused on associations between a polymorphism of the D2 dopamine receptor (DRD2) gene and alcohol dependence. However, the results of these studies are conflicting. Another receptor, the D3 dopamine receptor (DRD3), may be of additional interest since it is specifically located in the limbic area, and in particular in the nucleus accumbens which plays a significant role in the reward process of addiction behavior. We thus tested the association in three independent samples of alcoholic patients, with different origins and various inclusion criteria. No difference in the DRD3 gene polymorphism emerged between controls and alcoholic patients, regardless of their origin, inclusion criteria, or presence or absence of the DRD2 TaqI A1-allele. Despite the fact that more information could have been considered and that association studies provide limited information, there is good evidence that this DRD3 polymorphism does not play a major role in the genetic component of alcoholism.

Alcoholism↗
PubMed1995

Diagnosis of "sporadic" Huntington's disease.

The diagnosis of Huntington's disease (HD) in patients with progressive chorea and mental impairment, but without similarly affected relatives, remains uncertain and impedes genetic counseling. Twenty patients with suspected HD, but with no family history of the disease underwent molecular analysis of the CAG repeat in the IT15 gene for HD. Eighteen patients displayed the HD expanded allele and two had CAG repeats in the normal range. Neuropsychological tests could be performed in 12 of the 20 patients. Of these 10 with the expanded allele presented the deficits typical of HD, but not the two patients without the HD mutation. This study shows that a neuropsychological pattern is specific to patients with the expanded CAG and that most isolated patients with suspected HD are in fact affected.

Adult↗
PubMed1995

Sequence analysis of the CCG polymorphic region adjacent to the CAG triplet repeat of the HD gene in normal and HD chromosomes.

The CAG expansion responsible for Huntington's disease (HD) is followed by an adjacent polymorphic CCG repeat region which may interfere with a PCR based diagnosis. We have sequenced this region in 52 unrelated HD patients, from both normal and HD chromosomes. Fifty percent of the normal alleles were (CCG)7(CCT)2, 48% (CCG)10(CCT)2, and 2% (CCG)7(CCT)3. In contrast (CCG)7(CCT)2 was found in 85% of the HD alleles which represents significant linkage disequilibrium with the HD mutation.

Alleles↗
PubMed1995

Gender and age at onset in schizophrenia: impact of family history.

OBJECTIVE: The 1-year prevalence of schizophrenia was studied in a limited geographical area of Reunion Island (Indian Ocean) to assess the impact of family history of schizophrenia on the well-known association between gender and age at onset. METHOD: The population of schizophrenic patients meeting the DSM-III-R criteria for schizophrenia (N = 663) was identified and divided according to the presence of another schizophrenic patient among the first- and second-degree relatives. RESULTS: As previously reported, the median age at onset differed between the sexes: the males had an earlier onset (mean age = 27.8 years) than the females (31.5 years). Comparison of the ages at onset according to family history revealed that onset was later for female subjects with a negative family history than for the three other groups (i.e., males with or without a family history and females with a family history). No difference emerged in the comparison of the ages at onset of the males and females with a positive family history. CONCLUSIONS: Comparison of schizophrenic patients with familial versus sporadic disorder confirms the absence of a gender effect for age at onset in the subgroup with familial disorder. This approach also demonstrates the existence of a subgroup composed of affected females having late onset and no family history of schizophrenia.

Adolescent↗
PubMed1995

[Mucoviscidosis: comparative analysis of epidemiological data of French and North American registries].

A national registry for cystic fibrosis was established in France in 1993. A questionnaire is sent once a year to different health care units. The first questionnaire was analyzed in 1992: 1,893 patients (53% males) were identified. 28% were over 15 years of age, 13% more than 20, and 1% over 35. Usually, diagnosis had been suggested by respiratory signs, followed by digestive tract signs and growth impairment and meconial ileus. 13% were diagnosed in screening programmes. Diagnosis was made before 1 year in 66% of the subjects (mean = 7 months). All the data collected and the functional and bacteriologic data were compared with those observed in the United States and Canada. It should also be noted that 38 patients were grafted during this study year and that it is too early to analyze the general outcome for all subjects. The creation of this registry is an important step towards a better understanding of the epidemiology of cystic fibrosis in the French population.

Adolescent↗
PubMed1995

No evidence for genomic imprinting in liveborn Down syndrome patients.

Despite numerous studies, the clinical heterogeneity of Down syndrome has no explanation. The authors 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 polymorphic 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. The authors conclude that imprinting may probably not play a role in the heterogeneity of Down syndrome phenotype.

Adolescent↗
PubMed1995

[Role of genetic epidemiology in the study of infectious diseases. The example of malaria].

Genetic epidemiology is a new tool for the study of malaria, with interesting incidence in the comprehension of host/parasite interrelations. The existence of a co-dominant major gene, with a mendelian transmission, controlling the levels of parasitemia has been found out. This allele has a frequency of 24% which means that about 6% of the population is predisposed to high parasitemias. These studies show the interest to integrate the existence of a genetical variability in the development and the evaluation of malaria control programmes. They are offering new perspectives in therapeutics and in the elaboration of vaccinal strategies.

Animals↗
PubMed1995

Tandem peripheral blood progenitor cell transplants as initial therapy for metastatic breast cancer.

PURPOSE: To investigate the use of two sequential courses of high-dose chemotherapy and peripheral blood progenitor cell (PBPC) transplant as initial therapy for patients with untreated metastatic breast cancer. The goal of the study was to maximize treatment intensity through the use of two non-cross-resistant regimens, each equal in intensity to that used in single transplants. METHODS: PBPC were collected after a course of granulocyte colony-stimulating factor (G-CSF) only or of cyclophosphamide, etoposide, and G-CSF. The first transplant regimen consisted of thiotepa (600 mg/m2), cyclophosphamide (6000 mg/m2), and carboplatin (800 mg/m2). After recovery from the first transplant, responding patients received a second course of therapy consisting of busulfan (16 mg/kg) and etoposide (60 mg/kg). RESULTS: Forty-four patients were enrolled. Five patients did not proceed to transplantation due to tumor progression during PBPC mobilization. Five patients achieved complete response after the first transplant, and 14 were in complete remission at the end of the therapy. Six patients remain free of disease after a median followup of 22 months (range 12-27+ months). The 2-year event-free survival for complete responders is 25.4% (standard error 14.4%). Engraftment was prompt, with a median of 8 and 13 days, respectively, to reach a neutrophil count of 500/mm3 and a platelet count of 50,000/mm3. As a result of the gastrointestinal toxicity of the first course, the median interval between transplants was 68 days. The toxicities of the second transplant course were principally hepatic and muco-cutaneous. Hepatic veno-occlusive disease occurred in 12 patients and was a contributor to the death of three. CONCLUSIONS: Rapid hematologic recovery achieved with PBPC made possible the administration of two courses of high-dose chemotherapy without compromising the intensity of either transplant regimen. The adverse effects of the second course, however, were substantially higher than predicted. The outcome of patients achieving a complete response is promising. Overall, the antitumor benefit of this approach in patients with previously untreated metastatic disease was not superior to that achieved with single transplants in patients responding to standard-dose chemotherapy.

Adult↗
PubMed1994

Is Rett syndrome a chromosome breakage syndrome?

Lymphocytes from venous blood from 15 girls with Rett syndrome (RTS), 7 girls with RTS "forme fruste," and 46 unrelated control females were examined. All subjects had a normal karyotype using RHG and RTBG technique. The frequency of gaps and breaks was determined for each group. A significantly higher (P < 0.01) frequency of chromosome breakage was observed in RTS subjects compared to controls. This work suggests that an increased tendency to chromosome breakage may be part of a genetically determined disorder in RTS patients.

Case-Control Studies↗
PubMed1994

Parental consanguinity as a cause of increased incidence of birth defects in a study of 131,760 consecutive births.

The risk for birth defects in the offspring of first cousin parents is substantially higher than in the offspring of non-consanguineous parents. As a general decline in the frequency of consanguineous marriages was observed in this century, one wonders whether consanguinity is still a factor in the appearance of birth defects in developed countries. Based on our registry of congenital anomalies, we think that the answer to this question is "yes." In the population studied in Northeastern France, consanguineous matings were known in 1.08% of the cases with congenital anomalies, vs. 0.28% in controls (P < 0.001). The frequency of the malformations recorded paralleled the degree of consanguinity: out of 38 malformed children, 24 were seen in first cousin matings (10.5 times more frequent than in offspring of nonconsanguineous couples), 8 in second cousin marriages, and 6 in more distantly consanguineous matings. Consanguineous mothers were more often pregnant than nonconsanguineous mothers (P < 0.01) and they had more stillbirths than nonconsanguineous mothers. These results must be taken into account when counseling consanguineous couples.

Congenital Abnormalities↗