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Biomedical subjects

P J Wilson

Publications and source records attributed to P J Wilson.

11 recordsLinked to original sources
PubMed1992

Genetic mapping on the mouse X chromosome of human cDNA clones for the fragile X and Hunter syndromes.

Murine X-linked genes corresponding to the human Fragile X (FMR1) and Hunter syndrome (IDS) loci have been mapped in an interspecific backcross between B6CBA-Aw-J/A-Bpa and Mus spretus using human cDNA clones. Pedigree analysis of recombinants from a total of 248 backcross progeny favors a gene order of (Cf-9, Mcf-2)-(Fmr-1)-Ids-Gabra3-Rsvp. Gene order is conserved between the species, although no fragile site has been detected in the mouse in this region of the murine X chromosome.

Animals↗
PubMed1992

Molecular analysis of patients with Hunter syndrome: implication of a region prone to structural alterations within the IDS gene.

Hunter syndrome or mucopolysaccharidoses type II (MPS-II), is a lysosomal storage disorder caused by a deficiency in the activity of the enzyme iduronate-2-sulphatase (IDS). We have investigated the occurrence of rearrangements and deletions of the IDS gene in a Southern analysis of 46 unrelated MPS-II patients of different ethnic origins using a cDNA clone containing the entire IDS gene as a probe. Structural alterations of the IDS gene were found in DNA from 9 patients two of whom showed large deletions including all coding sequences of the gene. The distal and proximal breakpoint of these deletions were determined by hybridization of markers flanking the IDS gene. Seven of the observed alterations constitute major rearrangements of the gene. Interestingly, six of these rearrangements showed similar or identical patterns by Southern analysis suggestive for a region prone to structural alterations within the IDS gene. We also demonstrate the potential use of the IDS probe for carrier detection in families with a rearranged IDS gene. A contiguous gene deletion syndrome characterized by Hunter syndrome and epilepsy is also discussed.

Blotting, Southern↗
PubMed1992

Characterization of a deletion at Xq27-q28 associated with unbalanced inactivation of the nonmutant X chromosome.

We report the results of studies on the characterization of the mutation associated with marked unbalanced expression of the mutant X chromosome in a karyotypically normal girl with Hunter disease (mucopolysaccharidosis type II). Southern analysis of DNA extracted from somatic cell hybrids containing only the mutant X chromosome showed deletion of the Xq27.3-q28 loci: DXS297 (VK23AC), DXS293 (VK16), FRAXA (pfxa3), DXS296 (VK21A), and the 3' end of the iduronatesulfatase (IDS) gene. The flanking loci--DXS52 (St14-1), DXS304 (U6.2), and DXS369 (RN1)--were intact. On the basis of these results, we concluded that the mutation was a simple deletion extending a maximum of 3-5 cM to the centromeric side of the IDS gene. Both Southern analysis of DNA from somatic cell hybrids, using short segments of IDS cDNA, and PCR of reverse-transcribed RNA from cultured skin fibroblasts indicated that the telomeric terminus of the deletion was localized to a region near the middle of the coding sequences of the gene.

Autoradiography↗
PubMed1991

Frequent deletions at Xq28 indicate genetic heterogeneity in Hunter syndrome.

Hunter syndrome is a human X-linked disorder caused by deficiency of the lysosomal exohydrolase iduronate-2-sulphatase (IDS). The consequent accumulation of the mucopolysaccharides dermatan sulphate and heparan sulphate, in the brain and other tissues, often results in death before adulthood. There is, however, a broad spectrum of severity that has been attributed to different mutations of the Hunter syndrome gene. We have used an IDS cDNA clone to localise the IDS gene to Xq28, distal to the fragile X mutation (FRAXA). One-third of Hunter syndrome patients had various deletions or rearrangements of their IDS gene, proving that different mutations are common in this condition. Deletions of the IDS gene can include a conserved locus that is tightly linked to FRAXA, suggesting that deletion of nearby genes may contribute to the variable clinical severity noted in Hunter syndrome. The cDNA clone was also shown to span the X chromosome breakpoint in a female Hunter syndrome patient with an X;autosome translocation.

Blotting, Southern↗
PubMed1991

The clinical phenotype of two patients with a complete deletion of the iduronate-2-sulphatase gene (mucopolysaccharidosis II--Hunter syndrome).

Two patients with a complete deletion of the iduronate-2-sulphatase (IDS) gene are described. In both patients, the resulting phenotype was that of very severe Hunter syndrome (mucopolysaccharidosis II). In addition, both had features not commonly seen in this disorder, e.g. early onset of seizures in one patient and ptosis in the other. It is speculated that loss of adjacent loci may contribute to the unusual findings and that the severe features present in both patients may represent contiguous gene syndromes. Further analysis of IDS cDNA from other patients with Hunter's syndrome may eventually enable phenotype to be predicted more accurately.

Blotting, Southern↗
PubMed1991

Genetic mapping of new RFLPs at Xq27-q28.

The development of the human gene map in the region of the fragile X mutation (FRAXA) at Xq27 has been hampered by a lack of closely linked polymorphic loci. The polymorphic loci DXS369 (detected by probe RN1), DXS296 (VK21A, VK21C), and DXS304 (U6.2) have recently been mapped to within 5 cM of FRAXA. The order of loci near FRAXA has been defined on the basis of physical mapping studies as cen-F9-DXS105-DXS98-DXS369-DXS297-FRAXA-++ +DXS296-IDS-DXS304-DXS52-qter. The probe VK23B detected HindIII and XmnI restriction fragment length polymorphisms (RFLPs) at DXS297 with heterozygote frequencies of 0.34 and 0.49, respectively. An IDS cDNA probe, pc2S15, detected StuI and TaqI RFLPs at IDS with heterozygote frequencies of 0.50 and 0.08, respectively. Multipoint linkage analysis of these polymorphic loci in normal pedigrees indicated that the locus order was F9-(DXS105, DXS98)-(DXS369, DXS297)-(DXS293,IDS)-DXS304-DXS52. The recombination fractions between adjacent loci were F9-(0.058)-DXS105-(0.039)-DXS98-(0.123)-DXS369-(0.00)- DXS297-(0.057)-DXS296- (0.00)-IDS-(0.012)-DXS304-(0.120)-DXS52. This genetic map will provide the basis for further linkage studies of both the fragile X syndrome and other disorders mapped to Xq27-q28.

Female↗
PubMed1979

Functional budgeting.

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Attitude of Health Personnel↗
PubMed1975

Meningioma after contralateral hemispherectomy for malignant glioma: case report.

A patient is described who successfully underwent cerebral hemispherectomy for malignant glioma and whose death nine months later, wrongly ascribed to recurrent malignancy, was in fact due to a subsequently-developing benign meningioma in the remaining hemisphere. The possible advantages of a modification of standard hemispherectomy technique are also discussed.

Adult↗