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J Lejeune

Publications and source records attributed to J Lejeune.

At least 19 recordsLinked to original sources
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

Reduced sensitivity to dexamethasone of pancreatic islets from obese (fa/fa) rats.

The direct effects of dexamethasone exposure on insulin secretion from islets of fa/fa rats and their lean littermates (Fa/?) were compared. After 72 h culture in 1 nM dexamethasone, glucose (27.5 mM)-stimulated insulin secretion over 90 min from islets of lean rats was significantly decreased compared with islets cultured without dexamethasone (12.9 +/- 1.4 vs. 5.7 +/- 1.0% of total islet content, p < 0.05). Higher doses of dexamethasone for 24-48 h culture produced similar effects. For islets of fa/fa rats, the minimum inhibitory concentration of dexamethasone was 10-fold higher, and islets required at least 48 h exposure for inhibitory effects to be observed. Dexamethasone also decreased the insulin response by islets to glybenclamide, indicating that dexamethasone effects were not specific to glucose transport or metabolism. The results suggest that islets of fa/fa rats may be less sensitive to direct inhibitory effects of glucocorticoids on glucose-stimulated insulin release than islets of lean animals.

Animals↗
PubMed1992

No significant effect of monosomy for distal 21q22.3 on the Down syndrome phenotype in "mirror" duplications of chromosome 21.

Three Down syndrome patients for whom karyotypic analysis showed a "mirror" (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region--namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B--by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation.

Adult↗
PubMed1992

[Amino acids and trisomy 21].

The relative concentrations of plasmatic and urinary amino acids were analysed in 79 trisomic-21 patients, 322 mentally retarded non-trisomic patients, and 206 controls. No true amino acidopathy was found in 21-trisomy, but in plasma a deficit of serine and an excess of cysteine and lysine are highly significant. Excesses of cysteine, methionine, tyrosine, and methyl-histidine are also typical in urine. The increased activity of superoxide-dismutase, cystathionine-beta-synthase, and purine synthesis enzymes, together with the sensitivity to methotrexate, atropine, and dysthyroidism, are in accordance with this shift of equilibrium. A nutritional compensation seems worth investigating.

Amino Acids↗
PubMed1991

Metabolic anomalies in cri du chat syndrome (5p-) lymphocytes and de novo purine synthesis.

Having previously demonstrated that patients with cri du chat, 5p- syndrome, have a highly significant excess of the plasmatic and urinary relative amount of asparagine and aspartate, the authors tested the hypothesis according to which this excess could be in relation with a defect of purine metabolism. Using a previously reported in vitro assay, they found a paradoxal increase in the mitotic index in the presence of L-alanosine in lymphocyte cultures of patients with 5p- who were on no medication. They also observed particularly severe toxicity to HAT medium. This response, apparently characteristic for 5p- syndrome, was highly significant when compared to the one observed in samples of normal controls, of patients with mental retardation of various etiologies, patients with Down syndrome or with Xqfra syndrome. When patients with cri du chat syndrome received inosine with folinic acid, an inversion of their response to alanosine was observed as well as the normalization of their response to HAT medium. These findings suggest that deletion of 5p14-5p15 leads to some impairment of de novo purine synthesis, the implications of these findings are discussed.

Adolescent↗
PubMed1991

[The pathogenesis of mental retardation in trisomy 21].

An adequate number of nerve cells, their connection by dendrites and axons, the transmission of information by chemical mediators are all necessary for normal brain function. Monocarbonic acid residues, purines and pyrimidines and tubulins and biopterin are essential to ensure that the necessary chemical processes can take place. In trisomy 21 the metabolism is disturbed by the enhancement of individual enzyme activities. Particular clinical effects suggest specific therapeutic interventions. The effects can be influenced by way of the monocarbonic acid metabolisms. The action of thyroxine is especially interesting, as it inhibits the disintegration of monocarbonic acids.

Amyloid beta-Protein Precursor↗
PubMed1991

[Pathogenesis of mental impairment in trisomy 21].

Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially. A biochemical scheme of impairment of mental efficiency is presented, and the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S 100 beta protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterin metabolism interferences are reviewed. These metabolic paths are tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutual regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate, and systematic research of special sensitivities has begun. Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Re-equilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo Alzheimer complication is presented.

Chromosome Mapping↗
PubMed1990

Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain.

The plasma distribution of gallium (as an analogue of aluminium) was investigated in patients with Alzheimer disease, Down syndrome, or stroke dementia, in subjects on haemodialysis for chronic renal failure, and in healthy controls. Gallium-transferrin binding was significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%), whereas stroke dementia and haemodialysis patients had normal binding. There were no differences among the groups in plasma citrate concentration. The plasma transferrin concentration was slightly lower in the Alzheimer and Down syndrome groups than in the controls, but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98 [0.18] g/l in controls). Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%). This deficiency of gallium/aluminium binding would leave more unbound aluminium which could move readily into the brain, where it has neurotoxic effects.

Adult↗
PubMed1990

Pathogenesis of mental deficiency in trisomy 21.

In trisomy 21, pathogenesis of mental retardation is still poorly understood although the knowledge of the genic content of chromosome 21 is steadily increasing. Short of discovering how to silence selectively one of the 3 chromosomes 21, no rational medication can be envisaged before pathogenesis has been unraveled, at least partially. A biochemical scheme of impairment of mental efficiency is presented. Secondarily, the possible deleterious effects of a given gene overdose are discussed. Cu/Zn SOD, cystathionine beta synthase, S 100 beta protein, phosphofructokinase, purine synthesis and adenosine pharmacology, thyroid disturbance, and elevated TSH with low rT3 as well as biopterine metabolism interferences are reviewed. It is observed that the metabolic paths controlled by these genes, although unrelated at first glance, are in fact tightly related by their effects, just as if synteny was in some way related to biochemical cooperation or mutually controlled regulation. Experiments in vitro have demonstrated a peculiar sensitivity of trisomic 21 lymphocytes to methotrexate. From this starting point, systematic research of special sensitivities has begun. Clinical observations and relevant statistical methods allow study of the speed of mental development under various medications. The interest of regulating thyroid metabolism, when needed, is exemplified. Reequilibration of monocarbon metabolism is discussed and the seemingly favourable effect of folinic acid medication in pseudo-Alzheimer complication is presented.

Adolescent↗
PubMed1990

Risk of Down syndrome in relatives of trisomy 21 children. A case-control study.

We conducted a case-control study in families of Down syndrome children with classical trisomy 21 (n = 188) and in a control group of families of children referred to the same hospital for benign diseases (n = 185). The low sibling number does not allow any conclusion about the risk for sibs but our results do not support an increased incidence of Down syndrome among second and third degree relatives of trisomy 21 children. The choice of the control group and the restriction to close relatives protect us against biases which may have interfered in previous studies reporting recurrence in families.

Abortion, Spontaneous↗
PubMed1990

[r14 syndrome without major dysmorphism].

An 8-year-old boy, mentally retarded and epileptic since the age of six months, was found carrier of ring 14 chromosome. A dystrophy of the eye fundi was observed (whitish puncta of the macula); except for the "almond shaped eyes", there was no obvious dismorphism.

Abnormalities, Multiple↗
PubMed1990

[Cri-du-chat disease: plasma and urinary amino acids].

Ten cases of cri du chat disease due to a del(5)(p14p15) were observed. A highly significant excess of the plasmatic and urinary relative amount of asparagine + aspartate was detected. A highly significant excess of the relative amount of histidine was also noted in the urine but not in the plasma. Excess of asparagine + aspartate could be related to a disorder of purine metabolism. The urinary excess of histidine could be related to a disorder of the aminoacid catabolism.

Adolescent↗
PubMed1989

Structure of the gene of tum- transplantation antigen P91A: the mutated exon encodes a peptide recognized with Ld by cytolytic T cells.

Mutagen treatment of mouse P815 tumor cells produces immunogenic mutants that express new transplantation antigens (tum- antigens) recognized by cytolytic T cells. We found that the gene conferring expression of tum- antigen P91A contains 12 exons, encoding a 60 kd protein lacking a typical N-terminal signal sequence. The sequence shows no significant similarity with sequences in current data bases. A mutation that causes expression of the antigen is located in exon 4; it is the only apparent difference between the normal and the antigenic alleles. A short synthetic peptide corresponding to a region of exon 4 located around this mutation makes P815 cells sensitive to lysis by anti-P91A cytolytic T cells. The mutation creates a strong aggretope enabling the peptide to bind the H-2 Ld molecule. Several secondary tumor cell variants that no longer express tum- antigen P91A were found to carry deletions in the gene.

Amino Acid Sequence↗
PubMed1989

Absence of familial association between dementia of Alzheimer type and Down syndrome.

The aim of this study was to test whether there is an excess of dementia of Alzheimer type (DAT) cases in Down syndrome (DS) relatives. We conducted a case-control study in families of DS children with classical trisomy 21. A control group was constituted of families of children referred to the same hospital for benign diseases. Families of 188 DS children and 185 controls were recruited. We obtained vital statistics on 1,850 (response rate 82%) grandparents and great-grandparents in the DS group and 1,525 (69%) in the control group. Rates of possible severe dementia were calculated on ancestors over age 60 years with available data on mental function, 1,336 in the DS group and 1,113 in the control group. Rates of possible severe dementia were similar in the two groups: 5.6% (78 cases) in DS and 6.2% (66 cases) in control. Dementia with insidious onset suggestive of DAT was observed in 2% (28 cases) of DS ancestors and 2.6% (28 cases) of control ancestors. Our results argue against an excess of dementia cases with insidious onset suggestive of DAT in families of children with classical trisomy 21.

Age Factors↗
PubMed1989

Pure partial trisomy of the short arm of chromosome 5.

We describe a male infant with multiple dysmorphic features who is trisomic for chromosome segment 5p13.32----5p14.2 as a result of recombination aneusomy. His father is a balanced carrier of an inverted insertion of this chromosome segment. The clinical features of this patient are compared with those of other patients with isolated partial 5p trisomy reported in the literature.

Chromosome Banding↗