Search PubMed⌕ Search

Biomedical subjects

N Dahl

Publications and source records attributed to N Dahl.

At least 91 records · Page 5Linked to original sources
PubMed1993

Malignant osteopetrosis: c-src kinase is not reduced in fibroblasts.

Targeted disruption of the c-src gene leads to a severe form of osteopetrosis in mice [2]. As the c-src gene is expressed in all tissues and cells tested, we have analyzed fibroblasts from three individuals with malignant, congenital osteopetrosis for the expression of c-src at the protein level. No differences could be detected in c-src protein and c-src kinase activity levels between fibroblasts from healthy controls and affected individuals. Thus, impairment of c-src function as an etiological factor in human osteopetrosis appears unlikely in the individuals investigated.

CSK Tyrosine-Protein Kinase↗
PubMed1993

Intrafamilial variation in Leber hereditary optic neuropathy revealed by direct mutation analysis.

Leber hereditary optic neuropathy (LHON) has been associated with a mitochondrial mutation at position 11,778 in the ND4 gene in about 50% of families. Individuals from six Swedish families with LHON were investigated for the presence of this mutation using allele-specific oligonucleotides and a sensitive chemoluminescent detection system. The point mutation was seen in mitochondrial DNA extracted from leukocytes in five families, four of which showed a homoplasmic pattern. One family showed a heteroplasmic pattern and one family was negative for the mutation. Six adults without impaired vision from three LHON families were detected as carriers with a degree of mutated mitochondrial DNA similar to that in affected relatives. The results show that the penetrance of LHON varies remarkably among carriers of the 11,778 mutation within families. We conclude that the prognosis for carriers should be stated cautiously when interpreting results from mutation analysis of mitochondrial DNA in leukocytes.

Adult↗
PubMed1993

An irradiation-reduced hybrid panel for fine-structure mapping of the Xq28 region in the human genome.

Irradiation-reduced somatic cell hybrids containing fragments of the human X chromosome were constructed. Analysis of 16 hybrids that retained the Xq28 region with 12 Xq28-specific markers identified at least six different breakpoints, supporting the order cen-DXS304-DXS374-(DXS33, DXS134, DXS52, DXS15)-RCP-(DXS254, G6PD, F8C)-(DXS115, DXYS64)-qter. The generated panel of hybrids provides a useful tool for fine mapping of probes in the Xq28 region.

Animals↗
PubMed1993

Linkage mapping of a severe X-linked mental retardation syndrome.

A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy that hte disease loci of two other syndromes with overlapping clinical manifestations recently were shown by Turner et al. and Pettigrew et al. to be linked to markers at Xq26.

Abnormalities, Multiple↗
PubMed1992

Infantile autism--fragile X: molecular findings support genetic heterogeneity.

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression.

Adolescent↗
PubMed1992

Deletion of the Hunter gene and both DXS466 and DXS304 in a patient with mucopolysaccharidosis type II.

Hunter syndrome is an X-linked mucopolysaccharidosis due to deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). A cDNA clone containing the entire coding region of the human IDS gene, mapped in Xq28, has been used as molecular probe to study a patient with Hunter syndrome. A submicroscopic deletion has been detected that spans the IDS gene as well as DXS466 and DXS304, 2 loci mapped probably not more than 900 kb from the IDS locus. A detailed clinical description of the patient is provided and his phenotype is compared to that of other patients with IDS deletion described recently. By following the segregation of a restriction fragment length polymorphism at the IDS locus in the patient's family, our data suggest that the deletion occurred in the germ cells of the patient's grandfather.

Blotting, Southern↗
PubMed1992

Mutation analysis for prenatal diagnosis and heterozygote detection of Gaucher disease type III (Norrbottnian type).

A single base substitution in exon 10 of the glucocerebrosidase gene was detected in families affected by Gaucher disease (GD) type III. This mutation, which results in the substitution of proline for leucine in position 444 of glucocerebrosidase, has been shown to result in type III GD in a Swedish population. Three fetuses at risk for GD type III were diagnosed as homozygous for the mutation and the pregnancies were terminated. In a fourth pregnancy, one parent was excluded as being a carrier and the risk of having a child affected by GD was ignored. Direct analysis of common mutations causal to GD is now available and improves prenatal diagnosis in families where the molecular defect has been characterized.

Base Sequence↗
PubMed1992

Fracture patterns in malignant osteopetrosis (Albers-Schönberg disease).

We report the occurrence and distribution of 17 fractures in four patients with malignant, autosomal recessive osteopetrosis. The frequency of the disease in the Caucasian population is in the order of 1 per 20,000, of which the vast majority suffer from a mild autosomal dominant form. The patients have been followed up for 17-22 years and have multiple handicaps. Their case histories indicate that the lower extremity is the most common site for pathological fractures. The traumata were all caused by common accidents, usually falls. Conservative treatment was successful, with normal healing time in the four cases presented.

Adolescent↗
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

Circulating macrophage colony-stimulating factor is not reduced in malignant osteopetrosis.

Malignant osteopetrosis is a disorder characterized by a deficiency in osteoclast number or function. In one animal model of osteopetrosis, the op/op mouse, macrophage colony-stimulating factor (M-CSF) is absent, and the administration of M-CSF corrects the defects. We evaluated the serum of 13 patients with malignant osteopetrosis by an M-CSF radioimmunoassay to determine if a quantitative M-CSF deficiency existed in these patients. All patients had M-CSF present in levels equal to or higher than control serum. In addition, serum from 6 osteopetrotic patients was tested in a bioassay to determine if the M-CSF present is biologically active, and in all cases there was demonstrable activity in these samples. We provide evidence that deficiency of circulating M-CSF is unlikely to be a major contributor to the etiologic basis for the majority of children with malignant osteopetrosis.

Child, Preschool↗
PubMed1991

[The Norrbothnian type of Gaucher's disease. Mutation diagnosis as a simple technique for risk determination].

Direct analysis of monogenic disorders by means of DNA sequencing, both cDNA and genomic DNA, combined with functional studies, has enabled the molecular basis of a number of diseases to be determined. The development of DNA diagnostics is of particular importance in clinical medicine, and wellestablished methods are now available for the rapid and reliable detection of specific mutations. In the article are presented some of the techniques used, and their application in a few inherited disorders. Particular attention is focused on Gaucher's disease type III (the subacute neuronopathic or Norrbotten type), where a single mutation has been found to be present in all the Swedish cases investigated. The hereditary background of the disease, the basic molecular defect, and detection of the mutation are discussed.

Adult↗
PubMed1991

[Diagnosis of cystic fibrosis with DNA techniques].

The extensive body of genetic and physical mapping data accumulated since the identification of the cystic fibrosis (CF) gene locus on chromosome 7 has made possible the molecular cloning of the gene. A deletion of three DNA base pairs, removing a phenylalanine residue from position 508 of the protein product, accounts for 40-85 per cent of CF mutations in most Western countries, the estimated figure for Sweden being 60 per cent. In the article are discussed findings for three additional mutations (G551D, R553X and G542X), only one allele out of 200 analysed having been found to manifest the R553X mutation alone. Also discussed are DNA techniques for detecting the common mutation, recent progress toward in vivo correction of the defect, and indications and possibilities for future screening programs.

Adult↗
PubMed1991

Linkage relationship between incontinentia pigmenti (IP2) and nine terminal X long arm markers.

Linkage data for familial incontinentia pigmenti (IP2) and nine X chromosomal markers are reported. Previously found linkage between IP2 and the DXS52 locus is confirmed with the maximum lod score of 6.19 at a recombination fraction of 0.03. Linkage is also established with loci DXS134, DXS15 and DXS33. Multipoint analysis allows us to localize the IP2 locus outside a block of seven linked markers of the Xq28 region.

Chromosome Mapping↗
PubMed1991

A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1).

Amelogenesis imperfecta is characterized by the defective formation of tooth enamel. Here we present evidence that the X-linked form of this disorder (AIH1) is caused by a structural alteration in one of the predominant proteins in enamel, amelogenin. Southern blot analysis revealed a deletion extending over 5 kb of the amelogenin gene in males with the hypomineralization form of the AIH1. Carrier females were heterozygous for the molecular defect. The deletion appears to include at least two exons of the amelogenin gene and the extent of the deletion was verified by PCR analysis. The mutation was shown to segregate with the disease among 15 analyzed individuals belonging to the same kindred. Our results link a defect in the amelogenin gene to the abnormal formation of enamel. We thus conclude that the amelogenin protein has a role in biomineralization of tooth enamel.

Amelogenesis Imperfecta↗
PubMed1991

Linkage homogeneity near the fragile X locus in normal and fragile X families.

The fragile X syndrome locus, FRAXA, is located at Xq27. Until recently, few polymorphic loci had been genetically mapped close to FRAXA. This has been attributed to an increased frequency of recombination at Xq27, possibly associated with the fragile X mutation. In addition, the frequency of recombination around FRAXA has been reported to vary among fragile X families. These observations suggested that the genetic map at Xq27 in normal populations was different from that in fragile X populations and that the genetic map also varied within the fragile X population. Such variability would reduce the reliability of carrier risk estimates based on DNA studies in fragile X families. Five polymorphic loci have now been mapped to within 4 cM of FRAXA--DXS369, DXS297, DXS296, IDS, and DXS304. The frequency of recombination at Xq26-q28 was evaluated using data at these loci and at more distant loci from 112 families with the fragile X syndrome. Two-point and multipoint linkage analyses failed to detect any difference in the recombination fractions in fragile X versus normal families. Two-point and multipoint tests of linkage homogeneity failed to detect any evidence of linkage heterogeneity in the fragile X families. On the basis of this analysis, genetic maps derived from large samples of normal families and those derived from fragile X families are equally valid as the basis for calculating carrier risk estimates in a particular family.

Fragile X Syndrome↗