Anticipation (genetics)

About: Anticipation (genetics) is a research topic. Over the lifetime, 669 publications have been published within this topic receiving 21784 citations. The topic is also known as: Genetic Anticipation & Anticipation, Genetic.

Myotonic Dystrophy Protein Kinase: Structure, Function and Its Possible Role in the Pathogenesis of Myotonic Dystrophy Type 1

Abstract: Myotonic dystrophy protein kinase (DMPK) is a member of the AGC super family of serine/threonine protein kinases (Caenepeel et al, 2004; Manning et al, 2002) The DMPK human gene encodes several alternative spliced protein products believed to be involved in remodeling of the actin cytoskeleton, mitochondrial dynamics, ion homeostasis and nuclear envelope stability DMPK and its isoforms are mainly expressed in skeletal, heart and smooth muscle, and brain, the main targets of myotonic dystrophy type 1 (DM1) (Groenen et al, 2000; Ueda et al, 2000) DM1 is the most common form of muscular dystrophy in adults with a frequency of 1 in 8,000 individuals worldwide It is a multisystem dominantly inherited disorder characterized by myotonia, progressive muscular weakness and wasting, cardiac defects, cataracts and frontal balding, as well as several central nervous system (CNS) manifestations (Harper et al, 2002) The disease is caused by the expansion of an unstable (CTG)n repeat in the 3’-untranslated region (3’-UTR) of the DMPK gene (Brook et al, 1992; Fu et al, 1992; Mahadevan, M et al, 1992) In healthy population the CTG tract is polymorphic with alleles ranging from 5 to 37 in length Individuals carrying the DM1 premutation, a tract between 38 and 49 CTG repeats, generally are asymptomatic but are at risk of transmitting a pathological expanded mutation In contrast, a CTG expansion between 50 and 4000 CTG repeats results in DM1 disease Affected families show the phenomenon of anticipation; longer expansions correlate with an earlier age of onset and more severe course in subsequent generations Based on their clinical presentation DM1 is classified into four subtypes: late onset, classic DM1, childhood onset and congenital DM1 (CDM) (Harley et al, 1992) An RNA-mediated dominant gain-of-function is currently accepted as the pathogenic mechanism to explain features of the DM1 DMPK toxic transcripts accumulate as nuclear foci (Davis et al, 1997; Taneja et al, 1995), interfering with the activity of RNA-interacting proteins and altering RNA metabolism, notably the splicing programme (Ranum & Day, 2004) Although reduced DMPK protein levels in DM1 tissues

Palliative Hormonal Treatment in Endometrial Carcinoma

Abstract: At first sight the description of the palliative hormonal treatment methods in disseminated malignant endometrial tumors is a simple exercise requiring only a few minutes. This anticipation is true if only the presently established therapeutic models are described.

Exclusion of the expansion of CAG/CTG repeats at thirteen loci on chromosome 12 as a candidate genetic mutation in scapuloperoneal spinal muscular atrophy with anticipation

Abstract: Scapuloperoneal spinal muscular atrophy (SPSMA) is a neuromuscular disorder characterized by weakness in the distribution of shoulder girdle and peroneal muscles. We have previously described a large New England kindred with autosomal dominant SPSMA and have subsequently linked this family trait to 12q24.1-q24.31. In this family, disease expression becomes more severe and progressive in successive generations, suggesting genetic anticipation. Accordingly, we have investigated the thirteen known CAG/CTG repeat loci on chromosome 12 that could be tested by using the polymerase chain reaction as candidate genetic mutations in SPSMA. None of these loci is expanded.