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: The presentation of a young patient with symptoms ranging from developmental delay to movement disorders and ataxia requires that the physician involved in the child's care be aware of these diseases, their phenotypic variability, and their effects in previous generations.
Abstract: The relationship between the expansion of trinucleotide repeat sequences and human disease hs been the subject of a significant volume of study since the identification of a CGG repeat sequence in the mutated gene responsible for the fragile X syndrome. Six other neurologic diseases are now known to result from a triplet repeat expansion of either CTG or CAG nucleotides. Of particular interest to the pediatrician or pediatric subspecialist is the phenomenon of "anticipation," now clarified by mechanisms inherent to trinucleotide repeat expansions. The progressive enlargement of repeat sequences in successive generations of affected kindreds correlates inversely with the age of onset and, in some cases, the severity of the disease. The presentation of a young patient with symptoms ranging from developmental delay to movement disorders and ataxia requires that the physician involved in the child's care be aware of these diseases, their phenotypic variability, and their effects in previous generations. In this manner, pertinent history, including family history, may be obtained, relevant diagnostic testing initiated, and appropriate referrals facilitated.
12 citations
TL;DR: Clinical features of some familial cases of neurodegenerative diseases such as AD, ALS, and SCA1 are well correlated with their genetic mutations, suggesting a possible mechanism for the molecular basis of paternal anticipation of the disease.
Abstract: Clinical and molecular analyses of neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxia type 1 (SCA1) were performed. In the present study, a Japanese family of AD with an Ala285Val substitution in exon 8 of the presenilin-1 (PS-1) gene was found. This family was characterized by relatively late onset (mean age at 50 years) in familial AD with PS-1 gene mutation and by absence of myoclonus, seizure or paratonia. Magnetic resonance image (MRI) study showed marked linear signal abnormalities in white matter of parietoocctipital lobes, suggesting a presence of cortical amyloid angiopathy of the patient with PS-1 gene mutation. Clinical characteristics of familial amyotrophic lateral sclerosis (FALS) with four different missense point mutations in exons 2, 4, and 5 of the Cu/Zn superoxide dismutase (SOD) gene were reported. Although features of progressive neurogenic muscular atrophy was common in patients of these families, patients of each family showed characteristic clinical features. Although lower motor sign was evident in all cases, hyperreflexia varied from 0 to 100% among patients with the different mutations, and Babinski sign was not observed in any cases. Bulbar palsy was frequent with a mutation, but not present with another mutation. SOD activity of red blood cells was generally reduced with minor variations. CAG trinucleotide repeat expansion was analyzed in 25 families with hereditary ataxia of Menzel type in the northeast of Japan. Twenty of 38 patients in 12 families had expanded allele for spinocerebellar ataxia type 1 (SCA1). Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle or brain; sperm, however, showed an obvious expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. These results suggest that clinical features of some familial cases of neurodegenerative diseases such as AD, ALS, and SCA1 are well correlated with their genetic mutations.
12 citations
TL;DR: Clinical variation is so broad as to make the genetic diagnosis from clinical criteria alone practically impossible, the pathological definition of Machado-Joseph disease is more reliable, but some findings do overlap those of other genotypes.
Abstract: Background Clinical descriptions of the dominantly inherited ataxic motor syndromes in a 7-generation family of German origin were first reported in 1951. Objective To provide follow-up clinical, pathological, and genetic data for 9 patients in this family. Design Clinical histories and neurologic findings, gross and microscopic pathological features, and DNA analysis. Results Clinical presentations in this closely followed up portion of the family include fairly uniform ataxic and upper motor neuron symptoms. Nystagmus was a conspicuous and early sign, but generational anticipation was not evident. Although often present, amyotrophy was not a major source of disability. Major pathological degeneration was noted in the pons, spinal cord, and upper brainstem, where ubiquitin-immunoreactive intranuclear inclusion bodies were demonstrated. The diagnosis of Machado-Joseph disease ( SCA3 [spinocerebellar ataxia type 3] genotype) was established from autopsy tissue in 1 patient and from blood specimens in 6 others. Conclusions Clinical variation within this family and between this family and families with the SCA1 and SCA3 genotypes is so broad as to make the genetic diagnosis from clinical criteria alone practically impossible. The pathological definition of Machado-Joseph disease is more reliable, but some findings do overlap those of other genotypes. To our knowledge, the basis for the phenotypic variations in Machado-Joseph disease, genetic or otherwise, has not been established.
12 citations
TL;DR: The absence of genetic anticipation is consistent with the clinical similarity of familial and sporadic inflammatory bowel disease, and justifies the primary genetic analysis of familial disease under the assumption that their genetic background will be representative for all presentations of IBD.
12 citations
TL;DR: The finding suggests that BAFME and diseases with unstable expanding repeats, including those in non-coding regions, might share a similar molecular mechanism because such diseases often show clinical anticipation with maternal transmission.
Abstract: We recently reported clinical anticipation in Japanese families with benign adult familial myoclonus epilepsy (BAFME). However, it remains unknown whether clinical anticipation is predominantly associated with paternal or maternal transmission. We investigated the relationship between gender of the transmitting parent and clinical anticipation in nine BAFME families. Clinical anticipation regarding either cortical tremor or generalised seizures was observed in all 12 parent/child pairs (8 mother/child pairs and 4 father/child pairs). Moreover, a higher degree of clinical anticipation was associated with maternal transmission than with paternal transmission (p=0.03). Although a causative gene for BAFME still remains unknown, our finding suggests that BAFME and diseases with unstable expanding repeats, including those in non-coding regions, might share a similar molecular mechanism because such diseases often show clinical anticipation with maternal transmission.
12 citations