The Myotonic Dystrophy Gene

Pizzuti, Antonio; Dl, Friedman; Ct, Caskey

doi:10.1001/archneur.1993.00540110053005

Cited by 35 publications

(9 citation statements)

References 38 publications

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“…They are also subject to selection since they are linked to diseases (OMIN: On line Mendelian Inheritance in Man: http:www3.ncbi.nlm.nih.govomin), as are a number of HLA alleles. Microsatellites are more risky to use since their location in the genome is not always known, and their biological significance is sometimes doubtful (some of them are located in introns); in addition, their Mendelian inheritance does not always occur and they are often unable to define populations, probably because of their low degree of polymorphism (8–10).…”

Section: Definition and Genetic Markersmentioning

confidence: 99%

Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective

2002

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HLA genes allele distribution has been studied in Mediterranean and sub-Saharan populations. Their relatedness has been tested by genetic distances, neighbour-joining dendrograms and correspondence analyses. The population genetic relationships have been compared with the history of the classical populations living in the area. A revision of the historic postulates would have to be undertaken, particularly in the cases when genetics and history are overtly discordant. HLA genomics shows that: 1) Greeks share an important part of their genetic pool with sub-Saharan Africans (Ethiopians and west Africans) also supported by Chr 7 Markers. The gene flow from Black Africa to Greece may have occurred in Pharaonic times or when Saharan people emigrated after the present hyperarid conditions were established (5000 years B.C.). 2) Turks (Anatolians) do not significantly differ from other Mediterraneans, indicating that while the Asians Turks carried out an invasion with cultural significance (language), it is not genetically detectable. 3) Kurds and Armenians are genetically very close to Turks and other Middle East populations. 4) There is no HLA genetic trace of the so called Aryan invasion, which has only been defined on doubtful linguistic bases. 5) Iberians, including Basques, are related to north-African Berbers. 6) Present-day Algerian and Moroccan urban and country people show an indistinguishable Berber HLA profile.

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Section: Definition and Genetic Markersmentioning

confidence: 99%

Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective

2002

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“…inant gain-of-function mutation exerted at the RNA level Timchenko et al 1996). Repeat expansion may lead to reduction of poly(A)ϩ mRNAs (Carango et al 1993;Fu et al 1993;Hofmann-Radvanyi et al 1993;Pizzuti et al 1993; affecting DMPK gene expression at the posttranscriptional level (Krahe et al 1995). Transcripts from the mutant allele have been found, by DMPK mRNA-specific in situ hybridization analysis, to accumulate within intranuclear foci (Taneja et al 1995).…”

Section: Figurementioning

confidence: 99%

The DMPK Gene of Severely Affected Myotonic Dystrophy Patients Is Hypermethylated Proximal to the Largely Expanded CTG Repeat

Steinbach

Gläser

Vogel

et al. 1998

The American Journal of Human Genetics

100

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Using methylation-sensitive restriction enzymes, we characterized the methylation pattern on the 5' side of the CTG repeat in the DMPK gene of normal individuals and of patients affected with myotonic dystrophy, showing expansions of the repetitive sequence. The gene segment analyzed corresponds to the genomic SacI-HindIII fragment carrying exons 11-15. There is constitutive methylation in intron 12 at restriction sites of SacII and HhaI, localized 1,159-1,232 bp upstream of the CTG repeat, whereas most, if not all, of the other sites of SacII, HhaI, and HpaII in this region are unmethylated, in normal individuals and most of the patients. In a number of young and severely affected patients, however, complete methylation of these restriction sites was found in the mutated allele. In most of these patients, the onset of the disease was congenital. Preliminary in vivo footprinting data gave evidence for protein-DNA contact in normal genes at an Sp1 consensus binding site upstream of the CTG repeat and for a significant reduction of this interaction in cells with a hypermethylated DMPK gene.

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“…Recently our knowledge of MD has been increased to a considerable degree by remarkable molecular genetic and other advances [5,8,14,25,35,37,40,41].…”

Section: Introductionmentioning

confidence: 99%

Comparative morphometric evaluation of peripheral nerves and muscle fibers in myotonic dystrophy

Wang

Schröder

2000

Acta Neuropathol

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We compared peripheral nerve fibers and muscle fibers in myotonic dystrophy (MD) using a computer-assisted device for morphometry. In the 17 cases with MD studied, the sural nerves of 14 cases (82%) showed various degrees of reduction of the myelin sheath area (MSA) per endoneurial area. Of these, 8 cases (47%) presented with a mild reduction of the MSA, 5 cases (29.4%) with moderate reduction, and one case (6%) with severe reduction. The number of myelinated nerve fibers was not significantly reduced in MD when compared with control nerves, due to clusters of small regenerated nerve fibers. The mean diameter of the muscle fibers in 6 of the 17 cases was less than 40 microm. Of these 6 severely affected cases, 5 revealed a considerable reduction of the MSA. Other cases, which appeared to be normal in respect to the diameter of muscle fibers, showed various degrees of reduction of the MSA. Thus, there is usually, but not always a morphometric correlation of the severity of changes between peripheral nerves and muscle. The severity of the peripheral neuropathy appears to depend largely on the patient's age, the stage of the disorder, and the time of progression. Electron microscopic examination of sural nerves showed significant, though non-specific pathological changes.

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The Myotonic Dystrophy Gene

Cited by 35 publications

References 38 publications

Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective

Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective

The DMPK Gene of Severely Affected Myotonic Dystrophy Patients Is Hypermethylated Proximal to the Largely Expanded CTG Repeat

Comparative morphometric evaluation of peripheral nerves and muscle fibers in myotonic dystrophy

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