| 1. |
- Johansson, Jenni, et al.
(författare)
-
Expanded CAG repeats in Swedish Spinocerebellar ataxia type 7 (SCA7) patients : effect of repeat length on the clinical manifestation
- 1998
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 7:2, s. 171-176
-
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.
|
|
| 2. |
- Laporte, J., et al.
(författare)
-
Characterization of the myotubularin dual specificity phosphatase gene family, from yeast to human
- 1998
-
Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 7:11, s. 1703-1712
-
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.
|
|
| 3. |
|
|
