| 11. |
- Holmberg, Monica, et al.
(författare)
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Localization of autosomal dominant cerebellar ataxia associated with retinal degeneration and anticipation to chromosome 3p12-p21.1
- 1995
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 4:8, s. 1441-1445
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Tidskriftsartikel (refereegranskat)abstract
- We present linkage analysis on a large Swedish five-generation family of 15 affected individuals with autosomal dominant cerebellar ataxia (ADCA) associated with retinal degeneration and anticipation, Common clinical signs in this family include ataxia, dysarthria and severely impaired vision with the phenotype ADCA type II, Different subtypes of ADCA have proven difficult to classify clinically due to extensive phenotypic variability within and between families. Genetic analysis of a number of ADCA type I families shows that heterogeneity exists also genetically, During the last few years several types of ADCA type I have been localized and to date six genetically distinct forms have been identified including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph disease (MJD) (14q), SCA4 (16q), and finally SCA5 (11), We performed a genome-wide search of the Swedish ADCA type II family using a total of 270 microsatellite markers, Positive lod scores were obtained with a number of microsatellite markers located on chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod score of 4.53 achieved with the marker D3S1600. The ADCA type II gene could be restricted to a region of 32 cM by the markers D3S1547 and D3S1274.
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| 12. |
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| 13. |
- Johansson, Jenni, et al.
(författare)
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Expanded CAG repeats in Swedish Spinocerebellar ataxia type 7 (SCA7) patients : effect of repeat length on the clinical manifestation
- 1998
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 7:2, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia 7 (SCA7) is a neurodegenerative disorder characterized by degeneration of the cerebellum, brainstem and retina. The gene responsible for SCA7, located on chromosome 3p, recently was cloned and shown to contain a CAG repeat in the coding region of the gene, that is expanded in SCA7 patients of French origin, We examined the SCA7 repeat region in four Swedish SCA7 families as well as in 57 healthy controls, All Swedish SCA7 patients exhibited expanded CAG repeats with a strong negative correlation between repeat size and age of onset, The repeat length in SCA7 patients ranged from 40 to >200 repeats, The largest expansion was observed in a juvenile case with an age of onset of 3 months, and represents the longest polyglutamine stretch ever reported, In patients with 59 repeats or more, visual impairment was the most common initial symptom observed, while ataxia predominates in patients with <59 repeats. Two of the Swedish SCA7 families analysed in this study were shown to be related genealogically, The other two SCA7 families could not be traced back to a common ancestor, All four families shared the same allele on the disease chromosome at a locus closely linked to SCA7, suggesting the possibility of a founder effect in the Swedish population.
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| 14. |
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| 15. |
- Lagerstedt, Kristina, et al.
(författare)
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Double-strand breaks may initiate the inversion mutation causing the Hunter syndrome
- 1997
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 6:4, s. 627-633
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that patients with the Hunter syndrome frequently have suffered from a recombination event between the IDS gene and its putative pseudogene, IDS-2, resulting in an inversion of the intervening DNA. The inversion, which might be the consequence of an intrachromosomal mispairing, is caused by homologous recombination between sequences located in intron 7 of the IDS gene and sequences located distal of exon 3 in IDS-2. In order to gain insight into the mechanisms causing the inversion, we have isolated both inversion junctions in six unrelated patients. DNA sequence analysis of the junctions showed that all recombinations have taken place within a 1 kb region where the sequence identity is >98%. An interesting finding was the identification of regions with alternating IDS gene and IDS-2 sequences present at one inversion junction, suggesting that the recombination event has been initiated by a double-strand break in intron 7 of the IDS gene. The results from this study suggest that homologous recombination in man could be explained by mechanisms similar to those described for Saccharomyces cerevisiae. The results also have practical implications for diagnosis of patients with the Hunter syndrome.
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| 16. |
- Laporte, J., et al.
(författare)
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Characterization of the myotubularin dual specificity phosphatase gene family, from yeast to human
- 1998
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Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 7:11, s. 1703-1712
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Tidskriftsartikel (refereegranskat)abstract
- X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene. The corresponding protein, myotubularin, contains the consensus active site of tyrosine phosphatases (PTP) but otherwise shows no homology to other phosphatases. Myotubularin is able to hydrolyze a synthetic analogue of tyrosine phosphate, in a reaction inhibited by orthovanadate, and was recently shown to act on both phosphotyrosine and phosphoserine. This gene is conserved down to yeast and strong homologies were found with human ESTs, thus defining a new dual specificity phosphatase (DSP) family. We report the presence of novel members of the MTM gene family in Schizosaccharomyces pombe, Caenorhabditis elegans, zebrafish, Drosophila, mouse and man. This represents the largest family of DSPs described to date. Eight MTM-related genes were found in the human genome and we determined the chromosomal localization and expression pattern for most of them. A subclass of the myotubularin homologues lacks a functional PTP active site. Missense mutations found in XLMTM patients affect residues conserved in a Drosophila homologue. Comparison of the various genes allowed construction of a phylogenetic tree and reveals conserved residues which may be essential for function. These genes may be good candidates for other genetic diseases.
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| 17. |
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| 18. |
- Lind, L, et al.
(författare)
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Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3, to chromosome 15q21-q25.
- 1995
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Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 4:1, s. 109-12
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Tidskriftsartikel (refereegranskat)abstract
- Congenital dyserythropoietic anemia, type III (CDA III) is a rare autosomal dominant disorder characterized by macrocytic anemia, bone marrow erythroid hyperplasia and giant multinucleate erythroblasts. We have genetically characterized a large Swedish family in which the concurrence of CDA III and myeloma or benign monoclonal gammopathy is significantly higher than expected and have found that the causative genetic defect for CDA III maps to an 11 cM interval within 15q21-q25.
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| 19. |
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| 20. |
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