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.

Spinocerebellar Ataxia and Other Disorders of Trinucleotide Repeats

Abstract: Expansion of trinucleotide repeat sequences is now known to be the mutational mechanism in at least seven neurological disorders. These include fragile X syndrome, myotonic dystrophy (DM), spinobulbar muscular atrophy (SBMA), Huntington’ s disease (HD), Spinocerebellar ataxia type 1 (SCA1), dentatorubropallidoluysian atrophy (DRPLA), and Machado-Joseph disease (MJD). The discovery of trinucleotide repeat expansions provides a biological explanation for “anticipation,” a poorly understood clinical phenomenon frequently observed in these disorders. So far, only trinucleotide repeats with cytosine-guanine-guanine (CGG), cytosine-adenine-guanine (CAG), or cytosine-thymidineguanine (CTG) have been associated with disease states, although other polymorphic trinucleotide repeat sequences are widespread in the human genome (please see Addendum).

Anesthetic management of patients with pheochromocytomas: a report of three cases.

Abstract: The perioperative management of patients with pheochromocytoma is a challenge to even the most seasoned practitioner. Preoperative preparation, close monitoring, and anticipation of hemodynamic changes is critical for a successful outcome.

Applying polygenic risk scoring for psychiatric disorders within a family context

Abstract: We aim to investigate the application of polygenic risks scoring within a family context and thereby unravel role that common variation confers on disease risk within a pedigree that would have traditionally been viewed through the prism of monogenic inheritance only. We illustrate our discussion by analyzing polygenic risk scores for schizophrenia, major depressive disorder and bipolar disorder in a large pedigree (n~300) in which 30% of family members have major depressive disorder or bipolar disorder. The polygenic risk scores illuminate patterns of assortative mating and anticipation, whereby increased polygenic risk for psychiatric disorders is contributed by affected individuals who married into the family, thereby increasing genetic risk over generations in the family. This may explain the observation of anticipation in mood disorder, whereby onset is earlier and the severity of a disease increases over the generations of a family. Joint analyses of both rare and common variation may be the most powerful way to understand the familial genetics of mood and psychiatric disorders.

Anticipation in lymphoproliferative disorders.

Abstract: Anticipation denotes younger age at debut of a disease and/or increased severity in successive generations within a family. Anticipation cannot be explained from Mendelian mechanisms and, most likely, anticipation depends on epigenetic DNAmolecular mechanisms, e.g. trinuleotide repeats and partial DNA-methylation, FAS-mutations, influence of micro-RNA, parental imprinting or maternal affection from microchimerism during pregnancy. Pleiotrophy and anticipation are sometimes associated, as in families with lymphoprolifertive diseases (LPD), where knowledge on the initial germ-line mutation of the monoclonal expansion of cells for CLL, myeloma, non-Hodgkin’sand Hodgkin’s lymphoma and other diagnoses within LPD is strongly needed for the true understanding of disease, for proper counselling of the family and for the design of technology behind the future curative DNAmanipulation. In LPD, this primary mutation is apparently different from the cytogenetic abnormalities used for diagnostic purposes and caused by subsequent somatic mutations during the development of disease. In this issue of Leukemia & Lymphoma, Alexandrescu et al. [1] report and confirm a significant decline in the age at debut of disease in parent – offspring combinations of LPD with anticipation and pleiotrophy. It is a challenge to interpret such observations because they undoubtedly reflect and expose the mode of non-Mendelian molecular action [2]. The paper by Alexandrescu et al. shows the importance of looking at family histories to extract data for such studies. LPD-pedigree studies are in principle only possible when all patients and all healthy members of the family are known and the pedigree has been completed with extra-matrimonial off-springs, stillborns and when the pedigrees are seen in relation to the frequency of spontaneous, early abortions. Even the best organized registration of LPD cannot disregard minor faults in registration (e.g. from very old patients where LPD is a side diagnose or an unexpected finding at autopsy) and confusion over time about the true diagnosis since terminology and diagnostic criteria of LPD have been changed nearly every decade during the past 50 years (e.g. Rappaport-, Kieler-, Workingand WHO Formulations). This means in principle that each case of LPD must be reviewed, including crosschecks of old records and specimens from blood, bone marrow and tissue in those cases where such specimens are stored and available. In the present paper by Alexandrescu et al. [1] no such histological and diagnostic review was possible and any notion on lowand high-grade lymphomas was thus avoided, which does not exclude analysis of age-at-debut. The registration of data on healthy family members to patients with LPD must be approved by official and ethical authority. The rational for counting normal, healthy persons from National Registries with data on name, place of birth, age and control cross-check with the Cancer Registry and/or the Registry of Medical Diagnoses is: