Topic
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.
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TL;DR: This review describes a novel type of genome instability, expansion of trinucleotide repeats, and discusses the major breakthroughs in this field made during the last decade, with an emphasis on molecular models of repeat expansion.
Abstract: This review describes a novel type of genome instability, expansion of trinucleotide repeats. Orig- inally discovered in 1991 upon cloning the gene responsible for the fragile X syndrome, it has proved to be a general phenomenon responsible for a growing number of human neurological disorders. Besides apparent medical importance, the discovery of trinucleotide repeat expansion unraveled a fundamental problem of human genetics: a non-Mendelian type of inheritance called anticipation. Understanding the mechanisms of repeat expansion and the molecular pathways leading from these expansions to human diseases became a for- midable task for modern biology and one of its spectacular achievements. Here we discuss the major break- throughs in this field made during the last decade, with an emphasis on molecular models of repeat expansion.
25 citations
TL;DR: Clinical anticipation was observed in four families, which suggests the clinical progression over generation in Japanese BAFME families, and generalized seizures newly appeared in the next generation in those two families and in another family.
Abstract: The clinical anticipation in Japanese benign adult familial myoclonus epilepsy (BAFME), defined as earlier onset age of either cortical tremor or generalized seizures or new appearance of those symptoms in the next generation, remains unknown. The onset age and the degree of both cortical tremor and generalized seizures were investigated in nine patients of four BAFME families (mean age: 46.6 ± 18.7 years). Clinical anticipation in the onset age of cortical tremor or generalized seizures was observed in three families, and generalized seizures newly appeared in the next generation in those two families and in another family. Clinical anticipation was observed in four families, which suggests the clinical progression over generation in Japanese BAFME families.
25 citations
01 Jan 2001
TL;DR: Expansion of a CAG repeat localized near the amino terminus of ataxin-1 has been found to be the mutational mechanism in SCA1 and its size correlates inversely with the age of onset of symptoms and the severity of disease.
Abstract: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by ataxia, dysarthria and progressive bulbar dysfunction. The SCA 1 gene which maps to the short arm of chromosome 6 has been isolated using a positional cloning approach. The SCA1 transcript is 10660 bases and encodes a novel protein, ataxin-1, with a predicted molecular weight of 87 kDa. Expansion of a CAG repeat localized near the amino terminus of ataxin-1 has been found to be the mutational mechanism in SCA1. This CAG repeat is highly polymorphic with normal alleles containing 6-39 repeats. Individuals affected with SCA1 have one normal allele and one expanded allele containing 40-81 repeats. The size of the repeat correlates inversely with the age of onset of symptoms and the severity of disease. The repeat is a continuous CAG repeat tract on SCA1 chromosomes whereas in > or = 98% of normal alleles one or more CAT interruptions break the CAG repeat tracts into two tracts containing less than 18 repeats each. This suggests that loss of CAT interruptions within the SCA1 CAG repeat on normal chromosomes leads to triplet instability.
25 citations
TL;DR: A four generation family with O.D. in which anomalies such as syndactyly appear congenitally, whereas neurological signs and symptoms tend to be expressed in a more severe form and/or at an earlier age of onset in successive generations of the kindred is described.
Abstract: Oculodentodigital syndrome (O.D.) is an autosomal dominant disorder comprising facial anomalies, syndactyly, microcorneae, dental enamel hypoplasia, and leukodystrophy. We describe a four generation family with O.D. in which anomalies such as syndactyly appear congenitally, whereas neurological (i.e., leukodystrophic) signs and symptoms tend to be expressed in a more severe form and/or at an earlier age of onset in successive generations of the kindred. This pattern of phenotypic expression is consistent with the phenomenon of genetic anticipation, and we suggest that O.D. may be a trinucleotide repeat disorder.
25 citations
TL;DR: Results suggest genetic anticipation occurs in nodal osteoarthritis and if confirmed a search for trinucleotide repeats is warranted.
Abstract: OBJECTIVE—Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA).
METHODS—Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed.
RESULTS—The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p< 0.001) as was large joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p< 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents.
CONCLUSIONS—These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.
Keywords: nodal osteoarthritis; genetic anticipation; trinucleotide repeats
25 citations