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.

Anticipation or ascertainment bias in schizophrenia? Penrose's familial mental illness sample.

Abstract: Several studies have observed anticipation (earlier age at onset [AAO] in successive generations) in familial schizophrenia. However, whether true anticipation or ascertainment bias is the principal originating mechanism remains unclear. In 1944 L. S. Penrose collected AAO data on a large, representative sample of familial mental illness, using a broad ascertainment strategy. These data allowed examination of anticipation and ascertainment biases in five two-generation samples of affected relative pairs. The median intergenerational difference (MID) in AAO was used to assess anticipation. Results showed significant anticipation in parent-offspring pairs with schizophrenia (n = 137 pairs; MID 15 years; P = .0001) and in a positive control sample with Huntington disease (n = 11; P = .01). Broadening the diagnosis of the schizophrenia sample suggested anticipation of severity of illness. However, other analyses provided evidence for ascertainment bias, especially in later-AAO parents, in parent-offspring pairs. Aunt/uncle-niece/nephew schizophrenia pairs showed anticipation (n = 111; P = .0001), but the MID was 8 years and aunts/uncles had earlier median AAO than parents. Anticipation effects were greatest in pairs with late-AAO parents but remained significant in a subgroup of schizophrenia pairs with early parental AAO (n = 31; P = .03). A small control sample of other diseases had MID of 5 years but no significant anticipation (n = 9; P = .38). These results suggest that, although ascertainment-bias effects were observed in parent-offspring pairs, true anticipation appears to be inherent in the transmission of familial schizophrenia. The findings support investigations of unstable mutations and other mechanisms that may contribute to true anticipation in schizophrenia.

Studies of anticipation in bipolar affective disorder.

Abstract: Anticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.

Paternal transmission of the congenital form of myotonic dystrophy type 1: a new case and review of the literature.

Abstract: Myotonic dystrophy type 1 (DM1) is an autosomal dominant trinucleotide repeat disorder that shows anticipation. The mildest manifestations of the DM gene are usually noted in individuals with the smallest repeat sizes, while congenital myotonic dystrophy (CDM) is the most common clinical outcome of the larger expansions. For many years, it was thought that CDM could only be maternally transmitted. However, in the last few years, cases of paternal transmission of CDM have been described. We report a child with the CDM phenotype and 1, 800 CTG repeats born to an asymptomatic father with 65 repeats and compare this case to the four currently in the literature. We note that polyhydramnios was present in the majority of cases and that all fathers whose status was known had small repeat sizes and/or were asymptomatic at the time of their child's birth. Although it may be unusual, the possibility of the paternal transmission of CDM should be mentioned when counseling families with DM. The men who are at highest risk may be those who have small repeats sizes and are asymptomatic.

Anticipation in schizophrenia: new light on a controversial problem.

Abstract: Objective: Anticipation, recently found in several neuropsychiatric disorders, is an inheritance pattern within a pedigree in which disease severity increases or age at onset decreases in successive generations. Demonstration of genetic anticipation in schizophrenia could be of heuristic value, since unstable trinucleotide repeat DNA is known to he the biological basis of anticipation. However, to overcome one of the major ascertainment biases that might mimic anticipation-namely, the fact that patients in different generations are not interviewed at the same age, resulting in a greater chance offinding a later age at onset in the older generation-a new method of investigating anticipation was used. Method: The study subjects were 97 systematically ascertained schizophrenic patients belonging to 24 families with at least two generations affected who were identified during a 1-year prevalence study in a limited geographical area of Reunion Island (Indian Ocean). A method ofcalculating expected age at onset according to age at interview was used in the analyses. Results: In the younger generation of patients, the observed age at onset (2 1 . 80 years) was earlier than the expected age at onset (24. 95 years), demonstrating anticipation, even when five additional biases that can mimic this genetic effect-the proband effect, the presence of an affected father or mother, the bilineality of the illness, the fertility effect, and the cohort effect-were taken into account. Conclusions: Fyidence for anticipation was demonstrated in this group of schizophrenic patients. This may help the search for pathological genes implicated in the genesis of schizophrenia. (AmJ Psychiatry 1996; 153:1173-1177)

Macular degeneration associated with aberrant expansion of trinucleotide repeat of the SCA7 gene in 2 Japanese families

Abstract: Objective To evaluate the macular function of Japanese patients with a trinucleotide repeat expansion in the spinocerebellar ataxia type 7 ( SCA7 ) gene. Methods Ophthalmic findings in patients whose DNA analysis revealed expanded alleles of the trinucleotide repeat in the SCA7 gene were evaluated. Results Trinucleotide repeat was expanded from 40 to 48 in affected patients (control subjects, 12 repeats). Affected patients were characterized by different degrees of visual acuity decrease (0.09-0.9), a tritan axis color vision, a coarse granular appearance of the macular region on scanning laser ophthalmoscopy, depression of multifocal electroretinograms, and macular degeneration. However, pigmentary changes were not observed in the retina. The trinucleotide repeat was longer and the onset of macular dysfunction was earlier in the younger generation. One patient in a family manifested decreased visual acuity 10 years preceding other neurologic signs. Conclusions and Clinical Relevance Patients with SCA7 mutations showed macular dysfunction or degeneration with expansion of CAG repeat in the SCA7 gene. However, the lesions were less pigmented than those previously reported. Patients also showed ophthalmologic anticipation, which has not been reported for the ocular changes in other patients who have trinucleotide repeat expansion of the responsible genes.