Search PubMed⌕ Search

Biomedical subjects

J F Mattei

Publications and source records attributed to J F Mattei.

197 records · Page 11Linked to original sources
PubMedDate not supplied

Prader-Willi syndrome: diagnostic strategy with a cytogenetic and molecular approach.

Prader-Willi syndrome (PWS) is a disorder characterized by neonatal hypotonia with poor suck, mild to moderate mental retardation, obesity beginning after 3 yr of age, hypogonadism and characteristic facial features. High resolution cytogenetic studies showed a deletion of the proximal chromosome 15q(q11-q13) region in approximately 50%. Interestingly, the same deletion was described in another distinct mental disorder: the Angelman syndrome (AS). This deletion was confirmed by molecular analyses, and a new mechanism was reported: uniparental disomy (maternal in PWS and paternal in AS) strongly implicate genomic imprinting in this chromosomal region. The principal aim of our group is to apply cytogenetic and molecular biology techniques to perform diagnosis and genetic counselling. Patient studies were usually based on high resolution cytogenetic analysis, quantitative Southern blotting (with D15S9, D15S11, D15S10, D15S12 loci) and dinucleotide repeat polymorphism assay by polymerase chain reaction (PCR) (IR4 .3R and GABARB3). The combination of these different methods allowed us to propose a diagnostic strategy for PWS.

Angelman Syndrome↗
PubMedDate not supplied

Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male.

The fragile X-mental retardation syndrome is defined by a moderate to severe mental retardation associated with a cytogenetic marker, a fragile site localized on the long arm of the X chromosome at band Xq 27. This syndrome has recently been recognized as one of the major causes of genetically determined mental retardation, and as one of the most important X-linked diseases with respect to its frequency (analogous to that of Duchenne muscular dystrophy or of haemophilia A) and severity. In the absence of treatment, genetic screening for this disease would seem particularly important. Prenatal diagnosis is now feasible although difficult and detection of heterozygous carriers is only possible in approximately 50% of cases. The recent demonstration of genetic linkage between the glucose 6-phosphate dehydrogenase (G6PD)-colour blindness cluster (at Xq28) and the fragile X locus has suggested that the fragile site is indeed the site of the mutation. We show here that the fragile X and haemophilia B loci are closely linked, using as genetic marker a polymorphism of the coagulation factor IX gene. Our study of a large family has demonstrated transmission through a phenotypically normal male, a feature previously described in retrospective analysis of a few other fragile X pedigrees. Restriction polymorphisms associated with the factor IX gene should be useful for analysing this peculiar aspect of the genetics of the fragile X syndrome, and for genetic screening of the disease.

Adolescent↗
PubMedDate not supplied

The structural gene coding for myelin-associated proteolipid protein is mutated in jimpy mice.

Mutations affecting developmental processes may allow some insight into the complexity of the biological processes involved. In mice, two mutants that affect myelin formation in the central nervous system, jimpy and shiverer, have proved to be useful models for the study of this process. The predominant proteins in myelin are the major myelin proteolipid (PLP) and the myelin basic proteins (MBP), which together account for 80-90% of total myelin proteins. It has recently been shown that the shiverer mutation is located in the MBP structural gene, but the site of the jimpy mutation, which is X-chromosome-linked and may be similar to the sex-linked dismyelinization human disease, Pelizaeus-Merzbacher disease, remains unclear. Here we provide evidence, based on a combined genetic and biochemical approach, that the sex-linked recessive mutation jimpy is located in the structural gene coding for PLP.

Animals↗
PubMedDate not supplied

Phenotype-genotype correlation in 20 deletion and 20 non-deletion Angelman syndrome patients.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by the absence of a maternal contribution to chromosome 15q11-q13. There are four classes of AS according to molecular or cytogenetic status: maternal microdeletion of 15q11-q13 (approximately 70% of AS patients); uniparental disomy (UPD); defects in a putative imprinting centre (IM); the fourth includes 20-30% of AS individuals with biparental inheritance and a normal pattern of allelic methylation in 15q11-q13. Mutations of UBE3A have recently been identified as causing AS in the latter group. Few studies have investigated the phenotypic differences between these classes. We compared 20 non-deletion to 20 age-matched deletion patients and found significant phenotypic differences between the two groups. The more severe phenotype in the deletion group may suggest a contiguous gene syndrome.

Adolescent↗
PubMedDate not supplied

[Wilson's disease. A clinical and pathological study on 6 cases (author's transl)].

In connection with 6 cases of Wilson's disease, the authors recall the main features of this hereditary metabolic disorder at late onset (usually the second decade), treatable with a chelating agent, when diagnosed at an early stage. Wilson's disease is first of all a liver disease and the authors emphasize the fact that cirrhosis is usually present when neurologic symptoms, revealing the disease in 5 cases, appear, even if there is no clinical or biological evidence for liver disease. In one instance hemolytic anemia and chronic active hepatitis were observed at clinical onset. Copper metabolism usually gives the key for diagnosis but its interpretation may be difficult, a normal serum ceruleoplasmin level being found in two patients and evaluated at 6% in the literature. This fact brings up the puzzling question of the pathogesis of the disease. Wilson's disease is not a simple ceruleoplasmin synthesis defect, but a lysosomal disease responsible for the lack of copper biliary excretion. This is pointed out by histochemical studies using a special rubeanic acid preparation (revealing copper deposit on the biliary side of the hepatic cell), and by electron microscopy showing lysosomal dystrophy.

Adolescent↗
PubMedDate not supplied

[Asymetrical gonadal dysgenesis. Report of a case (author's transl)].

The authors report a case of asymetrical gonadal dysgenesis related to 45XO-46XY mosaicism in a 16 year old girl. Delayed, growth and puberty, Turner's dysmorphism without sexual ambiguity and skeletal abnormalities are the main clinical features suggesting the diagnosis. Exploratory laparotomy reveals infantil uterus, bilateral falopian tubes and streak gonads. A right dysgenetic testis is identified on electron microscopic examination. Theories on pathogenesis of this unusual genetic defect are discussed.

Adolescent↗
PubMedDate not supplied

[Contribution of in situ hybridization to chromosomal analysis].

In situ hybridization (ISH) is a new technique which allows localizing on chromosomes a molecule of DNA homologous to a given sequence of nucleic acids. It permits to improve the chromosomal analysis by marking any sequence of nucleic acids in interphase or metaphase. It opens new prospects for chromosomes mapping, study of evolution, chromosomal diagnosis, the role of oncogenes and chromosomal mechanics.

Biological Evolution↗
PubMedDate not supplied

[Thrombopenia and radial aplasia: 2 cases with platelet function and ultrastructural studies of megakaryocytes and platelets (author's transl)].

The authors report on two cases of congenital thrombopenia with radial aplasia. Both children display several birth defects and a mild thrombopenia; hemorragic manifestations occured in the first case only. Megakaryoblastic to platelets series, as studied with electronic microscopy, show small-sized, "microcytic" and hypogranular megakaryocytes, displaying a maturative disorder (dysmegakaryocytopoiesis). In functional studies, platelets of the first patient show an imperfect nucleotidic release and do not agregate normally with ristocetin. The second case exhibits mostly a PF3 reduction. The variety of expression of the megakaryocytic-platelets disorders appears likewise in the skeletal and visceral malformations. The whole disorder could be ascribed to a pleiotropic abnormal gene with a variable expressivity.

Blood Platelets↗
PubMedDate not supplied

[Medicine facing the challenge of genetics: from singular workshop to public health].

Medical genetics has established itself as a new field of medicine over the past 20 years. With its new techniques for artificial fertilisation, prenatal diagnosis and predictive medicine, it allows to control the quality of our children, raises the idealistic possibility of the perfect child, and already offers to predict the destiny of each of us. Going beyond the level of the individual in medicine, it implicates at the same time couples, families and indeed entire populations. It therefore provokes questions about the nature of man, his dignity and moral values. At this crucial point, it must have guides to prevent it becoming distanced from its essential vocation which is the medical treatment of human beings.

Confidentiality↗
PubMedDate not supplied

[46 XX karyotype men (author's transl)].

85 cases of this syndrom have been published since the original case in 1964. The main clinical symptoms are those of Klinefelter's disease from which it differs by the caryotype only. Azoospermie is the rule. 3 mechanisms can be implicated: Mosaic 46 XX/47 XY with secondary loss of Y chromosome; Translocation of a part of Y chromosome upon an autosome or Y chromosome; Autosomal mutant gene acting upon the masculinizing site of X chromosome and inducing the primitive development of the testis as the short arm and proximal part of the long arm of Y chromosome normally do. These mechanisms perhaps are distinct origins of a syndrom which clinic alone cannot dissociate.

Disorders of Sex Development↗