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J Feingold

Publications and source records attributed to J Feingold.

At least 127 records · Page 7Linked to original sources
PubMed1993

Genetic variation in transforming growth factor alpha: possible association of BamHI polymorphism with bilateral sporadic cleft lip and palate.

Non-syndromic cleft lip with or without cleft palate (CL/P) is one of the most common birth defects affecting 1/1000 Caucasians. Genetic factors are thought to contribute to the development of this disorder. A significant association between two restriction fragment length polymorphisms, the TGF alpha TaqI 2.7-kb allele and the TGF alpha BamHI 40-kb allele, at the transforming growth factor alpha (TGF alpha) locus and the occurrence of clefting has previously been reported. A total of 98 Caucasian patients of Alsacian ancestry was recruited from our registry of congenital malformations. These patients had isolated CL/P but no other anomalies. In addition 57 patients with cleft palate, but without cleft lip, were studied. A control group comprised 99 unrelated healthy Caucasians of the same Alsacian ancestry. TaqI and BamHI identify two-allele polymorphisms. The TGFA Taq and BamHI alleles showed no significant association with the presence of clefting, the only exception being that the BamHI 10.0-kb allele was significantly more frequent in patients with bilateral CL/P.

Child↗
PubMed1993

Phenotypic variability in autosomal dominant cerebellar ataxia type I is unrelated to genetic heterogeneity.

Families with autosomal dominant cerebellar ataxia (ADCA), a heterogeneous group of diseases, were investigated prior to and during genetic linkage analysis. We report here on the clinical features of 122 affected individuals from 36 unrelated families with ADCA type I, the most common type. Our results indicate an anticipation expressed in a mean 9.4 year earlier age at onset and more rapid clinical progression in successive generations. There was no imprinting, since age at onset, disease duration and severity of the disease were independent of parental transmission. Progressive cerebellar ataxia was variably associated with signs such as ophthalmoplegia, dysphagia, sphincter disturbances, briskness or loss of tendon reflexes, decreased vibration sense and amyotrophy, a variability correlated with disease duration. Linkage analysis of 10 informative families with microsatellite markers, located on the short arm of the chromosome 6, allowed the identification of four families showing positive linkage to the SCA1 (spinal cerebellar ataxia 1) locus and six non-SCA1 families for whom linkage to this locus was excluded. This reflects non-allelic genetic heterogeneity. Thus, the analysis of clinical signs associated with cerebellar ataxia in SCA1 versus non-SCA1 kindreds did not distinguish between the two groups. The clinical picture of ADCA type I did not reflect the genetic heterogeneity of the disease.

Adolescent↗
PubMed1993

Epidemiological and clinical study of sickle cell disease in France, French Guiana and Algeria.

The main clinical and haematological features of sickle cell patients were compared in 618 French, 50 Guianese and 87 Algerian patients. In homozygous sickle cell patients, the proportion of icteric subjects rises with age in all centres; the prevalence of splenomegaly reaches a peak in children from 1 to 5 years and then decreases; jaundice and splenomegaly are more often noted in Algerian and Guianese than French patients. The prevalence of painful crisis is comparable in the 3 centres. In 465 French SS children, having a mean age of 7.3 +/- 5.9 years, the prevalence of a past history of meningitis is 7.3%, of septicaemia 4.1% of osteomyelitis 8.8%. These percentages do not differ significantly between countries. Prevalence of a past history of cerebrovascular accident is 3.2% in French SS patients; 1.2% in SC, 3.8% in S beta thalassaemia. A past history of acute splenic sequestration was noted significantly more often in SS (11.75%) and S beta thalassaemia (14.3%) than SC (3.6%) in French children (p < 0.05). Proportions of subjects transfused at least once do not differ between countries; SS children are more transfused (64%) than SC (15.6%) and S beta thalassaemic (66%) (p < 10-4). Haemoglobin and reticulocyte counts do not differ significantly between countries. In conclusion, no major differences were detected between French, Guianese and Algerian homozygous sickle cell patients: this may be due to the fact that France is in itself a mosaïc of ethnic origins.

Adolescent↗
PubMed1993

Adrenoleukodystrophy in France: an epidemiological study.

An epidemiological study was conducted in France to estimate the prevalence of adrenoleukodystrophy, a severe neurologic X-linked disorder affecting boys and young men. 129 cases were collected. Analysis of all cases born between 1956 and 1986 with available clinical history allowed the calculation of the lowest estimation of the prevalence: 1 in 100,000 male births.

Adolescent↗
PubMed1993

Risk factors of malaria infection during pregnancy in Burkina Faso: suggestion of a genetic influence.

A cohort of 570 untreated pregnant women from Burkina Faso was studied to assess the influence of epidemiologic factors on malaria infection, which was quantified as the mean of serial, season-adjusted parasitemia measurements (mean parasite density [MPD]) carried out during the last five months of gestation. A significant effect of the area of maternal residence on the MPD was found (P < 0.003) and was probably due to geographic differences in mosquito transmission conditions. The strong relationship observed between parity and malaria infection (P < 0.0001), with MPD levels decreasing as the number of gestations increased, confirms that primigravidae are a high-risk group whose protection should be a priority. After adjustment for two relevant epidemiologic factors (i.e., area of residence and parity), the residual MPD values fitted a mixture of two distributions. This result supports the view that a major gene is involved in the determination of malaria infection intensities and is consistent with the results of a recent familial study in Cameroon.

Adult↗
PubMed1993

Huntington's disease in French families: CAG repeat expansion and linkage disequilibrium analysis.

The molecular defect causing Huntington's disease (HD) has been found as an expansion of CAG triplets in the 5' coding region of IT15 gene. In the 29 French families reported, the HD disease is due to the expansion of the CAG triplets region above 38 copies. The complete sequencing of 10 HD alleles PCR products allowed us to confirm that expansion is restricted to the CAG repeat region and does not extend to the adjacent CCG repeat region which is also present in the PCR product. Then, we analysed linkage disequilibrium between the molecular defect and 6 DNA markers mapping to the 4p16.3 region. The most striking finding in this study is the presence of a strong linkage disequilibrium between HD and D4S127 (PvuII), D4S95 (AccI, MboI, TaqI) located in a region of 130 kb distal to IT15 gene. Two major haplotypes, comprising D4S127 (PvuII) and D4S95 (MboI, AccI) polymorphic sites, were found in the normal population as only one was found associated with HD alleles. This result can be interpreted either as an evidence for a rather recent founder effect or as several independent mutations occuring in chromosomes bearing the same haplotype.

France↗
PubMed1993

Transforming growth factor-alpha: characterization of the BamHI, RsaI, and TaqI polymorphic regions.

We have characterized the nature of structural alleles of the transforming growth factor-alpha (TGF alpha) locus by restriction-enzyme digestion with BamHI, RsaI, and TaqI. The BamHI polymorphic site is located within exon VI, which codes for the 3' untranslated region. The two BamHI alleles differ by a single point mutation at the restriction site. The RsaI and TaqI polymorphic sites are located within intron V. The two alleles differ at the restriction site, either by a point mutation (RsaI) or by a 4-bp deletion (TaqI). This analysis permits us to devise a PCR method coupled with restriction digestions to directly identify the TGF alpha polymorphisms. Analysis of 99 Caucasian controls has revealed a highly significant (P < .001) association between the RsaI and the BamHI genotype. The frequency of the rare BamHI allele was significantly higher (P < .001) in transformed cell lines (.30) than in controls (.076).

Alleles↗
PubMed1993

[Conditions and limitations of healthy carrier screening for the mutation responsible for cystic fibrosis].

Cystic Fibrosis is an autosomal, recessive and lethal disease which affects one newborn in 2500 in most of European countries. The gene has been cloned and most of the deleterious mutations have been identified. This has led to a complete change in attitude to cystic fibrosis from a public health standpoint. Prenatal diagnosis is now available for couples of carriers (each unaffected parent carrying a deleterious mutation) with a 1/4 risk of having an affected newborn. Prenatal diagnosis can be performed through three different but complementary procedures with an overall reliability of 98%. As these couples at risk are identified by a first affected newborn, prenatal diagnosis may only prevent further ones. General screening of carriers would be valuable from a public health standpoint, for it could prevent the first affected newborn and would decrease very much the incidence of the disease. Such carrier screening is theoretically feasible through the direct analysis of identified deleterious mutations of the gene in the DNA of both parents, before any pregnancy. However there are major obstacles to general screening. On the one hand unidentified mutations are still numerous, except in certain populations, so screening is not perfect. On the other hand, the larger the number of tested mutations (and thus the better the efficiency of screening), the more expensive the procedure. New and cheaper screening technologies are therefore required but as yet unavailable. Moreover, due to the genetic variability within human populations, reliable screening can only be performed within certain homogeneous ethnic sub-populations. This limitation may raise ethical and public health questions.

Cystic Fibrosis↗
PubMed1992

Segregation of three reciprocal translocations in the same family: t(3;4), t(5;10), and t(15;21).

A male infant with static antenatal encephalopathy and epilepsy was found to have a duplication of 5p12----5pter and deficiency of 10p13----10pter. Each of his parents was a carrier of a balanced reciprocal translocation. A third translocation was found in the maternal grandfather. The pedigree of each translocation and the segregation of parental reciprocal translocations are discussed.

Amino Acids↗
PubMed1992

Clinical subtypes and age at onset in schizophrenic siblings.

This study examines the concordance of clinical subtypes and age at onset of schizophrenia in 42 sibships of multiply affected schizophrenic patients. Subtypes were defined by four major diagnostic systems (DSM-III, DSM-III-R, ICD-10, and Tsuang-Winokur criteria) and rated both for the first hospitalization and long-term diagnosis. When a sibship method was used, no concordance for subtypes was found in siblings. Age at onset, analyzed as a continuous variable with the intraclass correlation method, was found to be correlated in siblings. This finding suggest that the search for continuous traits distributed in families of schizophrenic patients might constitute an alternative to discrete category-based family studies.

Age Factors↗
PubMed1992

Evidence for a pseudoautosomal locus for schizophrenia. I: A replication study using phenotype analysis.

A locus for schizophrenia within the pseudoautosomal region of chromosomes X and Y has been suggested by Crow on the basis of epidemiological data. The present report replicates this finding in a sample of 38 French multiply affected families with schizophrenia. Sibship and pairwise analysis, with or without weighted-pair correction, with three different systems of family classifications, showed there to be an excess of same-sex pairs in paternally derived sibships, as predicted by the pseudoautosomal hypothesis.

Female↗
PubMed1992

Segregation analysis detects a major gene controlling blood infection levels in human malaria.

The profound influence that the genetic makeup of the host has on resistance to malaria infection has been established in numerous animal studies. This genetic heterogeneity is one of the main causes of the difficulties in developing an effective malaria vaccine. Segregation analysis is the first step in identifying the nature of genetic factors involved in the expression of human complex diseases, as infectious diseases. To assess the role of host genes in human malaria, we performed segregation analysis of blood parasite densities in 42 Cameroonian families by using both the unified mixed model and the class D regressive model of analysis. The results provide clear evidence for the presence of a recessive major gene controlling the degree of infection in human malaria. Parameter estimates show a frequency of .44-.48 for the deleterious allele, indicating that about 21% of the population is predisposed to high levels of infection.

Adolescent↗