Biomedical subjects

C Moutou

Publications and source records attributed to C Moutou.

23 records · Page 2Linked to original sources

PubMed1993

Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer.

We have undertaken a routine investigation of the p53 status for all the children treated at our institution either affected by multiple tumors or whose family displays at least one second degree relative or less, affected by cancer before the age of 45 years. We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood. A missense mutation affecting codons 248, 273, and 282 was identified in three families. The mutation was inherited in these three families and was detected in unaffected members. In seven families no mutation was detected in exons 5 to 8.

Adolescent↗

PubMed1993

Testing genomic imprinting in Wilm's tumor.

Data from 511 cases of Wilms' tumor in France (including 12 familial cases) and 8 pedigrees from the literature were analyzed to test three modifications of Knudson's classical bimutational theory, based on genomic imprinting in Wilms' tumor carcinogenesis. Analysis of data of age at diagnosis and segregation analysis were performed to determine the number of independent events for Wilms' tumor development and to search for a differential role of paternal and maternal alleles. Unexpectedly, we show that only one rare event is required for tumor development in isolated unilateral cases which are considered to be mainly nonhereditary. In familial cases, we observe no effect of the sex of the transmitting parent on either hge at diagnosis or segregation ratio. We show that this could be explained by models of genomic imprinting which assume two nonindependent events, or only one rare genetic event. In bilateral cases we show a bimodality for age at diagnosis which could be due to a mixture of hereditary and nonhereditary cases. This result completely questions the classical assumption according to which all bilateral cases would be hereditary. These findings support the hypothesis that this childhood cancer arises from a variety of etiological pathways and might be useful to find strategies for further molecular investigations.

Adolescent↗

PubMed1992

Genetics and epidemiology of Wilms' tumor: the French Wilms' tumor study.

A complete family history was obtained for 501 patients with Wilms' tumor, treated in departments of pediatric oncology in whole France. The information was collected by self-questionnaire and/or by interview of parents. The proportion of bilateral cases is 4.6% and there are 12 patients (2.4%) with a positive family history of Wilms' tumor. The affected relatives are most often distant and no first degree relative was affected. Apart from the well-known associations with aniridia, hemihypertrophy, genitourinary anomalies, Beckwith-Wiedeemann, and Drash syndromes, there is also a significant excess of congenital heart defects (P = .008) which remains to be explained. Several findings support the bimutational hypothesis such as earlier diagnosis and increased parental age in bilateral cases. No particular anomalies and no increased frequency of childhood cancer were found in patients' relatives. The frequency of Wilms' tumor in relatives was estimated to be less than 0.4% in sibs, 0.06% in uncles and aunts, and 0.04% in first cousins. These figures are very different from those found in retinoblastoma and suggest that the mechanism may be more complex in Wilms' tumor. This conclusion is in agreement with molecular biology studies in tumors and linkage analysis in multiple case families which suggest that more than one locus is involved.

Adolescent↗

PubMed1992

Beckwith-Wiedemann syndrome: a demonstration of the mechanisms responsible for the excess of transmitting females.

Beckwith-Wiedemann syndrome (BWS) is often associated with embryonal tumours (nephroblastoma, adrenocortical carcinoma, hepatoblastoma, and rhabdomyosarcoma). Several pedigrees have been reported strongly suggesting autosomal dominant inheritance and an excess of transmitting females was noticed in these families. We confirmed this excess using 19 published pedigrees and showed that this excess was for two reasons: first, reduced fecundity in affected males compared to females in a ratio of 1:4.6, and, second, a smaller risk of being affected in a ratio of 1:3 for subjects having inherited the gene from their father. These latter findings suggest genomic imprinting. Furthermore, considering these results together with other observations, such as the parental origin of the 15p15.5 duplication and the existence of uniparental disomy in some sporadic cases, we propose that overgrowth in BWS patients and malignant proliferation in associated tumours reflect an imbalance between paternal and maternal alleles.

Beckwith-Wiedemann Syndrome↗

PubMedDate not supplied

[Preimplantation genetic diagnosis of monogenic diseases].

Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis allowing the detection of genetic diseases on IVF embryos before their transfer into the uterus and before the pregnancy. The aim of this procedure is to obtain unaffected or carrier embryos in order to avoid the burden of termination of pregnancy after prenatal diagnosis for couples at risk of transmitting particularly severe genetic disorders to their offspring. For monogenic diseases, PGD is most often based on single blastomere amplification by polymerase chain reaction (PCR). More than a decade after the first births, the possibilities of diagnosis for monogenic diseases have considerably increased. As for molecular biology and conventional diagnosis, the technologies and strategies for PGD are continually improved, with for instance introduction of fluorescent PCR or multiplex amplification. In this review, we describe several approaches for PGD of monogenic diseases, followed by an overview of the French practice, particularly in our lab.

Chromosome Disorders↗