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Biomedical subjects

J Melki

Publications and source records attributed to J Melki.

66 records · Page 4Linked to original sources
PubMed1991

In situ hybridization of two markers closely flanking the spinal muscular atrophy gene to 5q12----q13.3.

In order to refine the physical location of the p105-153Ra and M4 probes which closely flank the spinal muscular atrophy gene (SMA) on human chromosome 5q, in situ hybridization has been carried out on prometaphase chromosomes. Our results demonstrate that the disease gene is located between the 5q12----q13.1 and 5q13.3 bands. The present study will hopefully contribute to microdissection of the chromosomal region of the SMA gene.

Child↗
PubMed1990

Mapping of acute (type I) spinal muscular atrophy to chromosome 5q12-q14. The French Spinal Muscular Atrophy Investigators.

Linkage analysis in twenty-five families with acute (type I) spinal muscular atrophy (SMA) showed that the mutant gene responsible for the disorder is tightly linked to the D5S39 locus. The mutation(s) causing the intermediate (type II) and juvenile chronic (type III) forms of SMA were also mapped to DNA marker D5S39 on chromosome 5 (5q12-q14). Thus, the three forms, which have been differentiated clinically on the basis of age of onset and clinical course, are most probably due to different mutations at a single locus on chromosome 5. Prenatal diagnosis of SMA type I will now be possible.

Acute Disease↗
PubMed1990

Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q.

Proximal spinal muscular atrophies represent the second most common fatal, autosomal recessive disorder after cystic fibrosis. The childhood form is classically subdivided into three groups: acute Werdnig-Hoffmann (type I), intermediate Werdnig-Hoffmann disease (type II) and Kugelberg-Welander disease (type III). These different clinical forms have previously been attributed to either genetic heterogeneity or variable expression of different mutations at the same locus. Research has been hindered because the underlying biochemical defect is unknown, and there are insufficient large pedigrees with the most common and severe form (type I) available for study. Therefore, we have undertaken a genetic linkage analysis of the chronic forms of the disease (types II and III) as an initial step towards the ultimate goal of characterizing the gene(s) responsible for all three types. We report here the assignment of the locus for the chronic forms to the long arm of chromosome 5 (5q12-q14), with the anonymous DNA marker D5S39, in 24 multiplex families of distinct ethnic origin. Furthermore, no evidence for genetic heterogeneity was found for types II and III in our study, suggesting that these two forms are allelic disorders.

Chromosome Mapping↗
PubMed1990

Rett phenotype with X/autosome translocation: possible mapping to the short arm of chromosome X.

Rett syndrome (RS) was diagnosed in a girl with a t(X;22) (p11.22;p11). This translocation was also present in her unaffected mother and her sister affected by a neurological disorder compatible with a "forme fruste" of RS. Different etiological mechanisms are considered: gene disruption, X inactivation disturbance, metabolic interference. Whatever this may be, the localization of a RS related gene to the short arm of chromosome X is likely.

Child↗
PubMed1990

An interstitial deletion in Xp22.3 in a family with X-linked recessive chondrodysplasia punctata and short stature.

In a four-generation family, chondrodysplasia punctata was found in a boy and one of his maternal uncles. These two patients also have short stature, as do all female members of the family, DNA molecular analysis of the pseudoautosomal and Xp22.3-specific loci revealed the presence of an interstitial deletion that cosegregates with the phenotypic abnormalities. The proximal breakpoint of this deletion was located distal to the DXS31 locus and the distal breakpoint in the pseudoautosomal region between DXYS59 and DXYS17. This maps the recessive X-linked form of chondrodysplasia punctata between the proximal boundary of the pseudoautosomal region and DXS31, and an Xp gene controlling growth between DXYS59 and DXS31.

Adult↗
PubMed1990

Usher syndrome type I is not linked to D1S81 (pTHH 33): evidence for genetic heterogeneity.

Usher syndrome is an autosomal recessive disease associating congenital sensorineural deafness and retinitis pigmentosa. Two clinical forms have been recognized, namely a) congenital and severe (type I) and b) later and moderate (type II). A linkage of the D1S81 probe (THH 33) with the gene for type II has been recently demonstrated by Kimberling et al. 1990. Here, a panel of 29 individuals from 6 kindreds with Usher syndrome type I has been tested for possible allelism at the D1S81 locus. A negative lod-score was found with this probe and close linkage to this region could be excluded. These different results support the view that the clinical heterogeneity in Usher syndrome is accounted for by an obvious genetic heterogeneity.

Blotting, Southern↗
PubMed1989

Nerve and muscle development in paralysé mutant mice.

Nerve and muscle development was studied in paralysé mutant mice. The mutant phenotype is first recognizable 6-7 days after birth (PN 6-PN 7) as cessation of muscle growth and weakness and incoordination of movement. Mutant animals die between 2 and 3 weeks of age. Muscle fibers from paralysé mutants had a unimodal distribution of diameters and normal numbers and distributions of acetylcholine receptors. The only structural abnormality seen was a reduced extracellular space within muscle fascicles. Total muscle choline acetyltransferase activity was reduced compared with that of control muscles, indicating that synaptic terminal development was impaired. Light and electron microscopy showed that polyneuronal innervation was retained in mutant endplates, and the normal process of withdrawal of redundant innervation did not occur. The paralysé muscles reacted to experimental denervation with an increase in extrajunctional acetylcholine receptor numbers. Intramuscular axons failed to become myelinated in mutant animals, although sciatic nerve axons were myelinated with a normal myelin thickness/axon diameter ratio. Nodes of Ranvier were elongated and myelin lamellae in the paranodal regions were poorly fused. Sciatic nerves in mutant animals retained the neonatal unimodal distribution of axon diameters, whereas in control animals it became bimodal by 2 weeks of age. Our results are not consistent with a previous suggestion that paralysé mutant muscle endplates are progressively denervated. We conclude that the major expression of the paralysé mutant phenotype is an arrest in development of both nerve and muscle during the first week after birth. The paralysé mutant gene most likely is involved in the general support of development of many or all body tissues from 1 week of age. We found no regression of any aspect of differentiation, once achieved.

Age Factors↗
PubMed1989

[Splenectomy in chronic idiopathic thrombopenic purpura in adults. Apropos of 49 cases].

The authors reviewed the case files of 49 adult patients undergoing splenectomy for chronic idiopathic thrombocytopenic purpura at the Centre Henri Becquerel between 1970 and 1987. Although the postoperative course was straightforward in 83.7% of cases, one reoperation for subphrenic abscess was necessary and there was one postoperative death. Remission from thrombocytopenia was obtained in 87.5% of the patients, but only transiently in 8.5% of them. No preoperative predictive factors could be demonstrated. An early postoperative rise in the platelet count to more than 500 G/litre appears to ensure a good subsequent result. Secondary infectious complications are not exceptional and can be fatal (one death in our series); they require prophylaxis by anti-pneumococcal vaccination. The place of prophylactic antibiotic therapy has yet to be defined.

Adolescent↗