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 in Menière's disease.

Abstract: The aetiology of Meniere's disease (MD) remains obscure, but is likely to be multifactorial, one of the factors being a genetic predisposition. Forty-one families with more than one living member with MD were ascertained and affected and normal relations examined. Blood was collected and DNA extracted and stored. In these families the mode of inheritance is autosomal dominant, the penetrance of the mutation being about 60 per cent. Some of the family members exhibit a partial syndrome, vestibular symptoms predominating. Sporadic and familial cases exhibit the same clinical features. The striking finding is the phenomenon of anticipation, whereby with successive generations there is an earlier age of onset and a tendency to more severe manifestation. The inference, considering that the cells which regulate endolymph are of neuroectodermal origin, is that, like other neurodegenerative disorders which show anticipation, MD manifestation is likely to be related to trinucloetide expansion within a gene.

Anticipation in familial Crohn's disease

Abstract: Background—OVspring with a family history of Crohn’s disease have an earlier age of onset than their parents. This might be due to genetic anticipation, characterised by earlier and/or more severe disease in subsequent generations. Aims—To investigate the possibility of genetic anticipation in aVected parentchild pairs with Crohn’s disease from France and Belgium. Patients and methods—In a cohort of 160 multiply aVected families with Crohn’s disease,57 parent-first aVected child pairs were detected. Clinical characteristics (age at diagnosis,disease extent,and type) of both parents and children were registered and compared. Results—Children were younger than their parents at diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p<0.0001). However, the diVerence was related to the age at diagnosis in the parents and was not present in 12 parentchild pairs with an early age at diagnosis for the parents. In most cases, disease extent and type were not considered more severe in children than in parents. Parental sex aVected neither age at diagnosis nor extent and type of disease in children. Conclusion—Patients in the second affected generation acquire their disease at an earlier time in life in some but not all familial cases of Crohn’s disease. Several explanations including genetic anticipation and environmental factors might explain this phenomenon. (Gut 1998;42:170‐174)

A clinical and molecular genetic study of dentatorubropallidoluysian atrophy in four European families.

Abstract: Dentatorubropallidoluysian atrophy is a neurodegenerative disorder with characteristic pathology, chiefly described in reports from Japan, and is associated with an unstable CAG trinucleotide repeat in a gene on chromosome 12. We describe four European families, three British and one Maltese, with this mutation. All exhibited autosomal dominant inheritance, and there was evidence for anticipation associated with an increase of the expansion with paternal transmission in two families. Affected chromosomes from patients with dentatorubropallidoluysian atrophy had CAG expansions of 58 to 74 repeats, compared to 7 to 26 in control chromosomes, and the size of repeat was significantly inversely correlated with age of onset. The clinical features were diverse, even within individual families, and comprised a combination of a movement disorder (chorea, myoclonus, dystonia, or parkinsonism), cerebellar ataxia, epilepsy, psychosis, and dementia. A clinical diagnosis of Huntington's disease had been made in affected individuals from all families. Neuropathological examination of 2 patients showed no specific abnormality in one and degenerative changes predominantly affecting the spinal cord in the other. Investigation of 55 patients who might represent sporadic examples of dentatorubropallidoluysian atrophy did not detect any expanded alleles. Dentatorubropallidoluysian atrophy is likely to be more common than previously recognized in non-Japanese populations, and should be considered in any patient with a dominantly inherited neurodegenerative disorder with the above-mentioned clinical features.

Myotonic dystrophy and proximal myotonic myophathy.

Abstract: Myotonic dystrophy (DM) is a well-known multisystem disorder with dominant inheritance. Proximal myotonic myopathy (PROMM) has been defined only recently, it is rather similar to but distinct from DM. Molecular genetic testing of the CTG trinucleotide repeat expansion is a reliable diagnostic method in DM. In PROMM these CTG repeats are normal, and no genetic test is so far available. Comparing the phenotypes of DM and PROMM, an important point seems to be that PROMM is a more benign disorder. There are almost no obvious mental changes in PROMM patients; premature death is extremely rare; anticipation appears to be present but to a milder degree; a severe congenital type of PROMM apparently is very rare if it occurs at all. On the other hand, at least in the German population, the frequency of PROMM may be almost equal to that of DM.