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C Wadelius

Publications and source records attributed to C Wadelius.

At least 55 records · Page 3Linked to original sources
PubMed1995

New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome.

The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function.

Abnormalities, Multiple↗
PubMed1994

Progress in a genome scan for linkage in schizophrenia in a large Swedish kindred.

Genetic linkage studies of a kindred from Sweden segregating for schizophrenia have been performed using a genetic model (autosomal dominant, f = 0.72, q = 0.02, phenocopies = 0.001) as described in Kennedy et al., 1988. Analyses of the restriction fragment length polymorphism (RFLP), allele-specific oligonucleotides (ASO), and short tandem repeat (STR also called microsatellite) data for 180 polymorphisms (individual probe-enzyme, ASO, or STR systems) at 155 loci have been completed using the MLINK and LIPED programs. Linkage to schizophrenia was excluded, under the given model, at 47 loci; indeterminate lod scores occurred at 108 loci. The total exclusion region across 20 chromosomes is estimated at 330 cM; 211 cM excluded by pairwise analyses and 119 cM previously excluded by multipoint analyses (Kennedy et al., 1989: Schizophr Bull 15:383-391; Moises et al. 1991: Genet Epidemiol 2:99-110; Hallmayer et al., 1992: Arch Gen Psychiatry 49:216-219).

Alleles↗
PubMed1994

The Sjögren-Larsson syndrome gene is close to D17S805 as determined by linkage analysis and allelic association.

Sjögren-Larsson Syndrome (SLS) is characterized by congenital ichthyosis, spastic dior tetraplegia and mental retardation. It is an autosomal recessive trait that is frequent in the northern part of Sweden. Based on linkage analysis and allelic association, the disorder has now been mapped to chromosome 17. Meiotic recombinations suggest that the gene is flanked by D17S805 on the centromeric and D17S783, D17S959, D17S842 and D17S925 on the telomeric side. These markers map to the same location in reference pedigrees. Strong allelic association (chi-square 60.28, p < 0.0003) to D17S805 suggests that the mutation is located close to this marker.

Alleles↗
PubMed1993

Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive skeletal dysplasia of unknown pathogenesis leading to short-limbed stature. Associated features include hypoplasia of hair, abnormal cellular immunity, deficient erythrogenesis, increased risk of malignancies, Hirschsprung disease, and Diamond-Blackfan type hypoplastic anaemia. We mapped the CHH gene by linkage analysis with 5 markers to chromosome 9. Multipoint linkage analysis gives a lod score of 9.94 for a location between D9S43 and D9S50. Based on strong linkage disequilibrium the closest marker, D9S50, is likely to be less than 1 cM from the gene. No heterogeneity was observed in 14 Finnish families, nor was there evidence of reduced penetrance. These results provide a starting point for the eventual cloning and characterization of the CHH gene.

Chromosome Mapping↗
PubMed1993

Deletion screening of Sri Lankan Duchenne muscular dystrophy patients using the polymerase chain reaction.

Duchenne muscular dystrophy (DMD) is an X-chromosome-linked myopathy caused by a defect in the DMD gene. Intragenic deletions appear to be the most common gene defect leading to DMD, and the deletion frequency has been estimated to be 66%. Results of this study using a group of 24 DMD patients of Sri Lankan origin employing the technique of multiplex DNA amplification using the polymerase chain reaction indicated a deletion frequency of 62.5%. Eighty per cent of these deletions were localized in a region of the DMD gene regarded as a 'hot spot' for DMD deletions. Our results are in agreement with the results of other studies carried out on Caucasian populations.

Gene Amplification↗
PubMed1993

Hemophilia B in a 46,XX female probably caused by non-random X inactivation.

A female whose father had severe hemophilia B was found to have a factor IX activity of about 1%. No chromosomal abnormality could be detected and DNA analysis gave no indications of deletions or mutations of Taq I cleavage sites in the factor IX gene. Analysis of the methylation pattern of locus DXS255 indicates that the expression of hemophilia B in this patient is caused by non-random X inactivation.

Blotting, Southern↗
PubMed1993

Autoimmune polyglandular disease type I. Exclusion map using amplifiable multiallelic markers in a microtiter well format.

The pathogenetic background of human autoimmunity is only partially understood. By discovering the defective gene causing the autosomal recessive polyglandular autoimmune disease type I (PGD I, APECED) we hope to provide new insights into autoimmune responses in general. Here we have taken advantage of newly developed amplifiable multiallelic microsatellite markers and performed the analyses using the microtiter well format of the polymerase chain reaction. This rapid semiautomated protocol was applied to analyze 62 assigned highly polymorphic loci. The linkage analyses coupled with the EXCLUDE analysis resulted in an exclusion map of this polyglandular autoimmune disease and in the preliminary assignment of the APECED locus to chromosome 22. The method proved to be an effective and economical tool for gene mapping compared with standard blotting and hybridization.

Alleles↗
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

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

Linkage analysis in properdin deficiency families: refined location in proximal Xp.

Properdin is a component of the alternative activation pathway of the complement system. Deficiency or dysfunction of the protein is inherited in an X-linked recessive manner. Affected males have an increased risk of developing meningococcal disease. Six multi-generation families with different types of properdin deficiency were analyzed using microsatellite and other polymorphisms on the X chromosome. Based on multipoint data, it was found that the disease gene maps close to DXS255 (Zmax = 13.3 at theta max = 0.00) and DXS426 (Zmax = 12.9 at theta max = 0.00) on the Xp-arm near the centromere. There was no indication of genetic heterogeneity among the six families analyzed. Thus it is now possible to perform accurate DNA-based determination of the inheritance of the mutation in affected families.

Chromosome Mapping↗
PubMed1992

The gene for Best's macular dystrophy is located at 11q13 in a Swedish family.

A large Swedish family with more than 250 cases of Best's macular dystrophy has been clinically and genetically studied. The gene was traced to a couple born in central Sweden in the 17th century. Highly significant evidence for genetic linkage to DNA markers on chromosome 11q13 was detected. A lod score of 15.12 was obtained at recombination fraction 0.01 with DNA marker INT2 (also called FGF3). The retinally expressed gene ROM1, which maps to the same chromosomal region is a candidate for this genetic disease.

Chromosomes, Human, Pair 11↗
PubMed1991

Evaluation of DNA-based diagnosis for haemophilia A.

Haemophilia A is an X-linked disorder affecting 1.7/10,000 males. Carrier detection in females and prenatal diagnosis of male foetuses is greatly improved by DNA-based diagnosis. This study describes the use of the polymerase chain reaction (PCR) and allele-specific oligonucleotides (ASO) in a clinical study comprising 190 individuals in 27 families. Prenatal diagnosis was performed in eight cases. Of three male fetuses, two were found to be affected and one unaffected. It is shown that 62% of women in the Swedish population are heterozygous for the intragenic BclI or XbaI polymorphisms and consequently a majority of them (53%) can be analysed in the PCR-based format. Using three intragenic polymorphisms, a combined heterozygosity of 64% was recorded in the females. If the extragenic loci DXS52 and DXS15 were used in addition, 97% of the women could be counselled by DNA-analysis. Our study demonstrates the usefulness of PCR-based analysis of the BclI- and the XbaI-polymorphisms in genetic counselling. The counselling of women with conflicting results between coagulation data and DNA-based linkage analysis is discussed.

Alleles↗
PubMed1991

Lowe's oculocerebrorenal syndrome--variation in lens changes in the carrier state.

The lens changes in DNA based analysis compatible carriers of the gene of Lowe's syndrome in one family are described. The lens changes consist of a large amount of characteristic punctate cortical opacities. In two of the three carriers, formed lens opacities were found, appearing like congenital riders. In one lens containing congenital-like riders a posterior subcapsular cataract had developed. In comparison with a previously examined family, the lens changes in the present family were overall much more extensive. It appears there is a variation in expressivity of the gene in carriers of different families.

Adult↗
PubMed1989

Isolation of a DNA probe of potential use for diagnosis of the fragile-X syndrome.

A new cloned DNA probe (U6.2), which recognizes polymorphisms near the locus for the fragile-X syndrome, was isolated. No recombinations were observed between the probe and the disease locus, although recombinations were observed with several other probes known to be located close to the fragile site. The locus defined by the probe, DXS304, cosegregated with the fragile-X phenotype in 29 informative meioses (zeta = 4.97, tau = 0.00). The degree of polymorphism at this locus and its proximity to the fragile-X locus makes it useful for carrier diagnosis and as a new starting point for attempts to clone the gene responsible for the disease.

DNA Probes↗
PubMed1989

Lowe oculocerebrorenal syndrome: DNA-based linkage of the gene to Xq24-q26, using tightly linked flanking markers and the correlation to lens examination in carrier diagnosis.

The Lowe syndrome (LS), or oculocerebrorenal syndrome, has been studied using DNA-based linkage analysis, and the findings have been correlated with the result of a thorough ophthalmologic examination. It was found that the LS gene was linked to markers in the Xq24-q26 region and that the locus DXS42 was the most closely linked marker, giving a LOD score of 3.12 at zero recombination distance. Combined with earlier data, this forms the basis for carrier detection and prenatal diagnosis by using tightly linked flanking markers. A summary of our and other data suggests that the loci DXS17, DXS11, DXS87, and DXS42 are located on the proximal side, and DXS86 and DXS10 on the distal side of the Lowe locus. In isolated cases of LS the question of whether the mother is a carrier of the mutation arises. It was found that a lens examination with slit-lamp illumination and a count of the total number of lenticular opacities is a reliable method of ascertaining the carrier state.

DNA Probes↗