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Biomedical subjects

S Gilgenkrantz

Publications and source records attributed to S Gilgenkrantz.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Probable localisation of the Coffin-Lowry locus in Xp22.2-p22.1 by multipoint linkage analysis.

The Coffin-Lowry syndrome (McKusick No. 30360) is a rare genetically transmitted disorder characterized by severe mental retardation, "coarse" facial appearance, thick soft skin, tapering fingers, and progressive skeletal abnormalities. X-linked inheritance is implied since the males are severely affected with variably mild manifestations in carrier women. We have performed a linkage analysis with many X-linked RFLP markers in 4 families. Positive two-point lod scores were obtained with DXS28 (z(theta) = 2.00 at theta = 0.05) and DXS41 (z(theta) = 1.26 at theta = 0.10). We performed a 5-point linkage analysis using the LINKMAP program assuming that DXS16 and DXS43 are a single locus and using the following fixed map (distances in centimorgans): DXS85 - 18cM - (DXS16, DXS43) - 13cM - DXS41 - 5cM -DXS28. This gave a multipoint lod score of 3.41 for a localisation in Xp22.2-p22.1, between DXS43 and DXS41.

Bone Diseases, Developmental↗
PubMedDate not supplied

New polymorphism and a new chromosome breakpoint establish the physical and genetic mapping of DXS369 in the DXS98-FRAXA interval.

Recently some of us cloned a new probe RN1 (DXS369), which appears a close marker for the fragile X locus (FRAXA) [Oostra et al.: Genomics 1990]. We present here new evidence for its physical and genetic mapping in the DXS98--FRAXA interval. We used 2 different somatic cell hybrid lines with breakpoints in the Xq27-q28 region: L10B Rea and PeCHN, and we established the order: (DXS105, DXS98)-L10B Rea-DXS369-PeCHN- (DXS304, DXS52). We detected an additional TaqI RFLP at the DXS369 locus which increases its informativeness up to 57%. Two point linkage analysis in a large set of families gave high lod scores for the FRAXA-DXS369 linkage (z(theta) = 10.1 at theta = 0.044) and for DXS369-DXS304, a marker distal to FRAXA (z = 19.2 at theta = 0.070). By multipoint analyses we established the localization of DXS369 in the DXS98-FRAXA interval. DXS369 is a much closer proximal marker for FRAXA than DXS105 or DXS98 and any new probe mapping between the breakpoints in L10B Rea and PeCHN will be of potential interest as a marker for FRAXA.

Adult↗
PubMedDate not supplied

Prenatal identification of a Y-chromosome deletion by Y-specific single copy DNA probes.

A sex chromosome deletion was identified in the course of prenatal diagnosis for maternal age. Ultrasound pictures revealed male fetal sex and a comparison with the father's Y chromosome suggested that the altered chromosome might be a de novo deletion of the Y chromosome. DNA hybridization with five human Y-specific probes shows that, among the Y-specific sequences recognized by the probes, only two of them are absent. The normal infant, at birth, was mosaic 46, XYq-/46,XY.

Adult↗
PubMedDate not supplied

Linkage study in a large pedigree with Stickler syndrome: exclusion of COL2A1 as the mutant gene.

A three generation family with Stickler syndrome is reported. Affected patients exhibited myopia with frequent retinal detachment or glaucoma. Most of them had characteristic facial dysmorphism, the Pierre-Robin sequence being observed in four individuals. Neonatal radiological signs of the Weissenbacher-Zweymüller syndrome were also noticed but early arthopathy was not reported in adults. Restriction fragment length polymorphism studies with the type II collagen gene (COL2A1) showed a recombination event between the disease locus and COL2A1, thus excluding collagen type II as the candidate gene. Although the calculation of the likelihood of genetic heterogeneity versus homogeneity based on 10 families was not statistically significant, we suggest that a second locus is probably involved in this highly variable syndrome.

Abnormalities, Multiple↗
PubMedDate not supplied

Myoblast transplantation between monozygotic twin girl carriers of Duchenne muscular dystrophy.

Monozygotic twin girls, both carriers of Duchenne muscular dystrophy, only one a severe symptomatic carrier and the other asymptomatic due to opposite lyonization, were studied. Myoblast clones were obtained from a muscle biopsy of the asymptomatic carrier. PCR amplification showed that most (94%) of these clones produced normal dystrophin mRNA. Roughly 704 million myoblasts were produced from 119 clones. These myoblasts were transplanted into the extensor carpi radialis (ECR) and in the biceps of one arm of the manifesting carrier while the other arm acted as the control. The strength of the patient was evaluated in a series of pre- and post-tests and a biopsy was obtained about 1 yr after the transplantation. The myoblast injections produced a significant force gain (12%-31%) in wrist extension but no force gain for elbow flexion. Muscle biopsies on the injected and control muscles obtained 1 yr after the injections showed only a small increase in the number of dystrophin positive fibers and the presence of numerous small type II fibers. The small beneficial effect of this transplantation cannot be attributed to immune problems, the donor and the recipient being identical twins, but may be due to a low level of spontaneous muscle regeneration.

Adolescent↗
PubMedDate not supplied

c-Ha-ras1 is not deleted in aniridia-Wilms' tumour association.

Non-random tumour-specific chromosomal abnormalities have been observed in cells of many different human tumours. In Wilms' tumour (WT) and retinoblastoma, a chromosomal deletion occurs germinally or somatically and has been considered an important step in tumour development. One class of potential cellular transforming genes comprises the cellular homologues of the transforming genes of highly oncogenic retroviruses. A remarkable concordance between the chromosomal location of human cellular oncogenes and the breakpoints involved in acquired chromosomal translocations is becoming apparent in various cancers: the oncogenes c-mos, c-myc and c-abl are located at the breakpoints that occur in acute myeloblastic leukaemia, Burkitt's lymphoma and chronic myelocytic leukaemia respectively. Thus when the oncogene c-Ha-ras1 was localized to the short arm of human chromosome 11 (refs 6-8; region 11p11 leads to p15 and not 11p13 as stated in ref. 5), it was proposed as a possible aetiological agent in the aniridia-WT association (AWTA) that results from a deletion of 11p13 (although a transforming gene recently isolated from a WT cell line (G401) was shown not to be homologous to either c-Ha-ras or c-Ki-ras9). We have now looked for deletion or rearrangement of c-Ha-ras1 in the DNA from four subjects with del(11p13)-associated predisposition to Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation. We report here that in no case is c-Ha-ras1 deleted, and we have further refined its location to 11p15.1 leads to 11p15.5. On the basis of enzyme studies and direct gene dosage determination for c-Ha-ras1 and beta-globin in neoplastic and non-neoplastic tissues from one patient, we conclude that deletion of the normal counterpart of 11p cannot account for the development of the tumour.

Child, Preschool↗