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.

Patient-Centered Therapy Development for Myotonic Dystrophy: Report of the Myotonic Dystrophy Foundation-Sponsored Workshop.

Abstract: Myotonic dystrophy (DM) is an autosomal dominant, repeat expansion, progressive disorder with no drug therapies. Consequently, to better define a regulatory pathway in anticipation of new treatment strategies under investigation, the Myotonic Dystrophy Foundation convened a workshop entitled "Patient-Centered Therapy Development for Myotonic Dystrophy" in September 2015. Participants included representatives from academia, industry, the patient community, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). Presenters described the symptom burden of the disease, and existing data on DM biomarkers, endpoints, natural history, and benefit-risk considerations. FDA participants helped clarify the regulatory requirements for new drug treatment approvals and DM-specific issues such as variability, slow progression, and low prevalence. Workshop attendees gained a better understanding of DM and the current status of existing data and tools to support therapeutic drug research and development.

[Clinical variability of Juvenile Huntington's Disease phenotype].

Abstract: Huntington's disease is rare, genetically determinated, neurodegenerative disorder. It is determined by dynamic mutation of IT15 gene on short arm of 4 chromosome. Characteristic symptomatology include involuntary movements, cognitive decline and wide spectrum of mood and behaviour disorders. It typically becomes noticeable in mid-adult life, but there are reported cases of appaers of symptoms between 2 and 80 year of life. Especially interesting is juvenile Huntington's disease- the Westphal variant with the beginning in childchood (before 20 year of age) because of clinical differences causing diagnostic difficulties. It affects 5-10% of carries of the mutant gene. Symptoms became noticeable before 10 year of age only in 1% of them.

Clinical characteristics of Huntington disease in two pedigrees and analysis of expanded CAG trinucleotide repeat

Abstract: Objective To understand the clinical and genetic features of Huntington disease (HD). Methods The clinical data of HD cases from 2 Chinese families were analyzed and trinucleotide repeat in the IT15 gene were investigated in 9 of the two families by polymerase chain reaction and GeneScan. Results Among the two pedigrees, 6 cases were ascertained as HD by genetic test. Genotypes of IT15 were heterozygous in these HD patients. CAG repeat of the patients in the HD chromosome were 40-78. In the two pedigrees, the onset age was earlier in the subsequent generations than that of their fathers. In pedigree 2, the onset age was inversely correlated with CAG repeat number. One out of the 6 cases was juvenile-onset type of Huntington disease, whose clinical symptoms were different from those of the adult-onset cases, especially the hypertonic manifestation. Conclusion HD is an autosomal dominant neurodegenerative disorder with genetic anticipation caused by enlargement of CAG repeat in IT15 gene. The clinical manifestation is different between the juvenile-onset and the adult-onset. The number of CAG repeat is inversely correlated with the onset age and clinical severity.

[Juvenile form of Huntington's disease--diagnostic problems].

Abstract: Variability of clinical manifestation is an important feature of Huntington's disease (HD). It is due to the high instability of CAG sequences within a coding region of IT15 gene. We present five pedigrees in which apart from the adult form of HD the juvenile form of the disease affected some of the patients--as a result of genetic anticipation. Molecular analysis confirmed the well known fact that anticipation, which manifests itself by earlier onset of the disease in the subsequent generations, is strongly correlated with the degree of amplification of (CAG)n repeats in IT15 gene. An interesting feature of the presented data is the fact, that expansion of CAG repeats occurred not only at the paternal but also at the maternal transmission of the mutation. Some children in the presented HD pedigrees presented other neurological disturbances which could be suspected of HD; a molecular analysis revealing normal number of CAG repeats, enabled us to avoid misdiagnosis. The presented data provide evidence that clinical diagnosis of HD, particularly in cases with not very characteristic clinical picture--is not possible without DNA analysis--even in the families undoubtfully affected with the disease.

Anticipation inFamilial Leukemia

Abstract: Summary Anticipation refers toworsening severity orearlier age atonset witheachgeneration foraninherited disease andprimarily hasbeendescribed forneurodegenerative illnesses resulting fromexpansion oftrinucleotide repeats. Wehavetested forevidence ofanticipation in familial leukemia. Of49affected individuals innine families transmitting autosomal dominant acute myelogenous leukemia (AML), themeanageatonset is57 years inthegrandparental generation, 32years inthe parental generation, and13years intheyoungest generation (P< .001). Of21parent-child pairs withAML, 19showyounger ages atonset inthechild anddemonstrate ameandecline inageatonset of28years (P <.001). Of18affected individuals fromseven pedigrees withautosomal dominant chronic lymphocytic leukemia(CLL), themeanageatonset intheparental generation is66years versus 51years intheyoungest generation (P= .008). Ofnineparent-child pairs withCLL, eight showyounger ages atonset inthechild andreveal ameandecline inageatonset of21years (P= .001). Inspection ofrare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types ofleukemia, andlymphoma isalso compatible withanticipation. Sampling bias isunlikely toexplain these findings. Thissuggests that dynamic mutation of unstable DNA sequence repeats could beacommon mechanism ofinherited hematopoietic malignancy with implications fortherole ofsomatic mutation inthemore frequent sporadic cases. Wespeculate onthree possible candidate genes forfamilial leukemia withanticipation: alocus on21q22.1-22.2, CBL2on11q23.3, andCBFB oranearby gene on16q22.