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Biomedical subjects

C Junien

Publications and source records attributed to C Junien.

At least 109 records · Page 6Linked to original sources
PubMed1991

Uniparental paternal disomy in a genetic cancer-predisposing syndrome.

The 11p15.5 region of human chromosome 11 seems to contain a locus or loci involved in congenital overgrowth anomalies as well as in the genesis of many tumours associated with the Beckwith-Wiedemann syndrome (BWS). Given the unusual differential parental allele involvement in the different aetiological forms of BWS and the loss of maternal alleles in associated tumours, we have now used 11p15.5 markers to determine the parental origin of chromosome 11 in eight sporadic cases of BWS. Probands in three informative families had uniparental paternal disomy for region 11p15.5. Further, an overall greatly increased frequency of homozygosity for several 11p15.5 markers in 21 sporadic BWS patients suggests that isodisomy probably accounts for an even higher proportion of BWS sporadic cases. This demonstrates that uniparental paternal disomy can be associated with a genetic cancer-predisposing syndrome.

Beckwith-Wiedemann Syndrome↗
PubMed1991

[Mechanism of parathyroid cell proliferation in primary hyperparathyroidism].

In primary hyperparathyroidism molecular biology techniques applied to the pathological parathyroid tissue have shown that cell proliferation is monoclonal in many sporadic adenomas and in the largest parathyroid glands of multiple endocrine neoplasia type 1 (MEN-1). On the other hand, monoclonality has not been found in sporadic hyperplasia and in the smaller parathyroid glands of MEN-1. In addition, abnormalities have been observed in chromosome 11 which contains the parathyroid hormone (PTH) gene and the MEN-1 associated gene. The PTH gene was rearranged in sporadic adenomas, and there was a varying degree of chromosome 11 allele delection in sporadic adenomas and in MEN-1. The relationship between these abnormalities and parathyroid cell proliferation is controverted, and further studies are required to determine their exact role in the development of primary hyperparathyroidism.

Cell Division↗
PubMed1991

[Primary hyperparathyroidism. Mechanisms of hypercalcemia].

In primary hyperparathyroidism, hypercalcaemia is due to inappropriate hypersecretion of parathormone (PTH). Yet, the intestinal or osseous origin of the excess in plasma calcium and the symptoms of the disease are largely conditioned by vitamin D reserve and metabolism. In cases with sufficient vitamin D reserve and normal metabolism, the primary disorder is hyperabsorption of calcium by the intestine, and there is a risk of renal stone formation. In patients with vitamin D deficiency, there is a significant increase of bone resorption accompanied by osteoarticular symptoms. In addition, other factors, as yet unidentified, seem to intervene in the reabsorption of calcium by the renal tubule, which commands the degree of hypercalcaemia. Hypersecretion of parathormone may be due either to a reduced sensitivity of parathyroid cells to calcium (as in adenomas) or to an increase of the PTH-secreting thyroid mass (as in hyperplasia and some adenomas).

Adenoma↗
PubMed1991

Recurrent mutation at aa 792 in the LDL receptor gene in a French patient.

Many mutations in the low density lipoprotein receptor gene (LDLR) have been characterized at the molecular level in individuals with familial hypercholesterolemia. Most of the mutations that have been reported are large deletions or insertions in the gene, it being much more difficult to identify point mutations. In this study, 139 unrelated French familial hypercholesterolemia subjects were screened for the presence of three different previously described LDLR point mutations, employing the polymerase chain reaction and allele-specific oligonucleotide hybridization. Only one subject carried a point mutation at amino acid position 792, which substituted a Trp codon for a Stop codon. The same mutation has previously been described in a subject originating from Saudi Arabia. Haplotype analysis of LDLR associated with each mutation was performed. The haplotypes were totally different, suggesting that this mutation has occurred more than once.

Base Sequence↗
PubMed1991

The distal region of 11p13 and associated genetic diseases.

The distal region of human chromosome band 11p13 is believed to contain a cluster of genes involved in the development of the eye, kidney, urogenital tract, and possibly the nervous system. Genetic abnormalities of this region can lead to Wilms tumor, aniridia, urogenital abnormalities, and mental retardation (WAGR syndrome). Using 11 DNA markers covering the entire distal region of 11p13, including the WAGR region, we have carried out molecular studies on 58 patients with one or more features of this syndrome and patients with other diseases or structural cytogenetic abnormalities associated with 11p13. Cytogenetic analyses were performed in all cases. In 12 patients we were able to demonstrate deletions of this region. In 2 patients balanced translocations and in 2 additional patients duplications of this region were characterized. In total, 5 chromosomal breakpoints within 11p13 were identified. One of these breakpoints maps within the smallest region of overlap of WAGR deletions. Moreover, we were unable to demonstrate constitutional deletions in a candidate sequence for the Wilms tumor gene or any other marker in 2 patients with aniridia and urogenital abnormalities, 4 patients with Wilms tumor and urogenital abnormalities, 5 patients with bilateral Wilms tumors, and 3 familial Wilms tumor cases. We suggest that the molecular techniques used here (heterozygosity testing for polymorphic markers mapping between AN2 and WT1 and deletion analysis by dosage, cytogenetic analysis, or in situ hybridization) can be employed to identify sporadic aniridia patients with and without increased tumor risk.

Adolescent↗
PubMed1991

Prenatal diagnosis of myotonic dystrophy using closely linked flanking markers.

We report on two cases of prenatal diagnosis of myotonic dystrophy (DM), using flanking markers APOC2 or CKMM on the proximal side and D19S51 on the distal side. By double digestion (TaqI and NcoI) of PCR amplified CKMM, the informativeness was increased from a PIC value of 0.57 to 0.69. Altogether, with a PIC value of 0.64 for APOC2, 0.69 for CKMM, and 0.27 for D19S51 (BglI), presymptomatic and prenatal diagnosis can thus be offered to approximately 24% of persons with a risk between 0.0004 and 0.0008 using these flanking markers.

Adult↗
PubMed1991

Anderson's disease: genetic exclusion of the apolipoprotein-B gene in two families.

Anderson's disease is a recessive disorder characterized by intestinal fat malabsorption, absence of postprandial chylomicrons, and reduced levels of cholesterol, triglycerides, and apoproteins B, AI, and C. We have studied two families with, respectively, three and two children with Anderson's disease. Intestinal apo-B and apo-AIV mRNAs from two Anderson's patients were normal in size but their concentration was decreased fivefold compared with controls. After DNA digestion with seven restriction enzymes, restriction fragment length polymorphisms of apo-B gene did not show conclusive information except for Xba1, which revealed a lack of cosegregation between the restriction fragment length polymorphism and the Anderson's phenotype. Linkage analysis was performed using the polymorphism of the apo-B gene 3'minisatellite. Genomic DNA from parents and children was amplified by polymerase chain reaction using oligonucleotide primers flanking the apo-B gene 3'hypervariable locus. In both families each child inherited different apo-B alleles from at least one parent. According to the recessive mode of transmission of the disease, our results are incompatible with the involvement of the apo-B gene. More likely a posttranslational defect or a mutation in another gene encoding a protein essential for lipoprotein assembly or secretion may be involved.

Adolescent↗
PubMed1991

[Molecular genetics of heart diseases. A familial approach].

Cardiovascular diseases are the result of the interaction of genetic and environmental factors and constitute a complex group of monogenic and, above all, polygenic pathologies. The possibility of localising the responsible genetic factors on the chromosomes by the study of families may eventually enable a predictive diagnosis, better orientation of treatment and a fuller understanding of the interaction of the different cardiovascular risk factors. The family approach allows the confirmation or the elimination of the role of a given gene of major or minor expression because of the polymorphisms of DNA.

Chromosome Aberrations↗
PubMed1991

[Antioncogenes: models for tumors in children].

The chromosomal assignment of genes responsible for malformation syndromes associated with increased susceptibility to malignancy could be determined owing to specific constitutional chromosomal abnormalities or to family studies. For certain types of tumors, somatic chromosomal rearrangements (loss of alleles) occur at the same locus indicating the presence of a recessive suppressor gene or an antioncogène. For other types of tumors chromosomal rearrangements involving regions different from the locus for predisposition suggest genetic heterogeneity and/or implication of genes for tumor progression. These genes which are also involved in development and regulation of differentiation and cell growth, may undergo a differential genomic imprinting.

Alleles↗
PubMed1990

The human MyoD1 (MYF3) gene maps on the short arm of chromosome 11 but is not associated with the WAGR locus or the region for the Beckwith-Wiedemann syndrome.

The human gene encoding the myogenic determination factor myf3 (mouse MyoD1) has been mapped to the short arm of chromosome 11. Analysis of several somatic cell hybrids containing various derivatives with deletions or translocations revealed that the human MyoD (MYF3) gene is not associated with the WAGR locus at chromosomal band 11p13 nor with the loss of the heterozygosity region at 11p15.5 related to the Beckwith-Wiedemann syndrome. Subregional mapping by in situ hybridization with an myf3 specific probe shows that the gene resides at the chromosomal band 11p14, possibly at 11p14.3.

Animals↗
PubMed1990

Constitutional and somatic deletions of two different regions of maternal chromosome 11 in Wilms tumor.

Loss of heterozygosity for 11p markers and preferential loss of maternal alleles have been described in Wilms tumor. In this report we describe the molecular characterization of the constitutional and somatic 11p rearrangements in a del(11p13) WAGR patient with Wilms tumor. Both rearrangements led to loss of maternal alleles for two different regions of 11p, namely, 11p13 and 11p14----p15. This result clearly suggests that Knudson's hypothesis of two hits at the same locus does not necessarily apply to Wilms tumor. Moreover, the loss of 11p15 maternal alleles in the tumor is not incompatible with maternal inheritance of predisposition at 11p13. The putative roles of these two loci are discussed.

Alleles↗
PubMed1990

Role for the Wilms tumor gene in genital development?

Detailed molecular definition of the WAGR region at chromosome 11p13 has been achieved by chromosome breakpoint analysis and long-range restriction mapping. Here we describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT). The region of overlap between this deletion and one associated with WT and similar genital anomalies but no aniridia covers a region of 350-400 kilobases, which is coincident with the extent of homozygous deletion detected in tumor tissue from a sporadic WT. A candidate WT gene located within this region has recently been isolated, suggesting nonpenetrance for tumor expression in the first individual. The inclusion within the overlap region of a gene for WT predisposition and a gene for the best-documented WT-associated genitourinary malformations leads us to suggest that both of these anomalies result from a loss-of-function mutation at the same locus. This in turn implies that the WT gene exerts pleiotropic effect on both kidney and genitourinary development, a possibility supported by the observed expression pattern of the WT candidate gene in developing kidney and gonads.

Aniridia↗
PubMed1990

Linkage analysis of five fibrillar collagen loci in a large French Marfan syndrome family.

Marfan syndrome consists of a group of dominantly inherited disorders of connective tissue with wide clinical variability. Using the candidate gene approach, we have attempted to map the gene defect in a large French Marfan syndrome family with no ocular manifestations. We performed linkage studies with polymorphic probes for five structural procollagen genes. The data obtained exclude linkage of Marfan syndrome to the two major fibrillar collagen (COL1A1, COL1A2, and COL2A1) genes. These results confirm previously published data obtained from smaller pedigrees. A small positive lod score (Z = 0.99, theta = 0.00) was obtained for the COL3A1-COL5A2 gene cluster located on chromosome 2.

Chromosome Mapping↗