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.

DNA analysis of a pedigree with myotonic dystrophy in Songjiang county, Shanghai.

Abstract: OBJECTIVE To make the molecular analysis of a pedigree with myotonic dystrophy (DM) in Songjiang county, Shanghai, and to observe the connection between CTG repeat number and clinical features. METHODS In twenty-three individuals of a pedigree with DM, CTG trinucleotide repeat numbers located in the 3' untranslated region of a protein kinase gene (MTPK) on chromosome 19q13.2-3 were analyzed by using Long Expand TM Template PCR system. RESULTS Four of eight clinical patients had expanded DM allele, the other four had no expanded CTG copies. Seven of eight suspicious DM cases had expanded CTG repeat numbers and were therefore genetically diagnosed as DM, and an asymptomatic individual was diagnosed as a doubted DM patient by DNA analysis. High risk of DM in six of seven individuals was ruled out, and a clinical doubted DM individual was ascertained a normal person by molecular analysis. A positive correlation was found beween early onset and expanded CTG repeat number in six parents (or grandparents)/child pairs, but in the pair II 2 /IV 7 CTG repeat numbers were reduced from 3100 in the grandmother to 175 in her grandson and there was no anticipation phenomenon. CONCLUSION The measurement of CTG repeat number can help to ascertain the diagnosis of DM in clinical and preclinical patients, but some clinically- diagnosed DM patients might have normal CTG repeat numbers. Anticipation phenomena were common in the pedigree.

[IT15 gene analysis in two pedigrees of Huntington's disease].

Abstract: To investigate the relationship between the clinical features and (CAG)n trinucleotide repeats in two pedigrees of Chinese Huntington's disease (HD). Clinical and neuroimaging features, the age of disease onset and pattern of transmission of the patients were studied in the two pedigrees of HD. Genomic DNA of 42 family members was used for amplification of the (CAG)n repeats of IT15 gene by PCR. The numbers of (CAG)n were determined by electrophoresis through a 6% polyacrylamide gel and direct sequence analysis. Results showed that patients in pedigree 1 were absent of the typical triad of HD symptoms or caudate atrophy. A total of 9 (5 patients and 4 asymptomatic) out of 18 family members had 40-50 (CAG)n repeats in the IT15 gene. In pedigree 2, all the patients were characterized by a triad of symptoms, including motor disturbance, cognitive impairment and psychiatric features. Three patients and two asymptomatic relatives had more than 50 (CAG)n repeats in the IT15 gene. In conclusion, the clinical symptoms are partly determined by (CAG)n repeats in the IT15 gene. The age of onset was correlated with (CAG)n repeats over 50, and the phenomenon called "anticipation" was found to have played a role.

Ataxia and progressive encephalopathy in a 4-year-old girl

Abstract: The spinocerebellar ataxias (SCAs) are a rare group of neurodegenerative disorders with progressive cerebellar ataxia as the primary feature. These disorders are phenotypically and genetically variable, both between and within subtypes. Seven of the SCA subtypes are caused by CAG trinucleotide repeats within the respective genes, and clinically most of these diseases demonstrate anticipation. Testing for these disorders typically relies upon conventional polymerase chain reaction (PCR) and fragment analysis. However, conventional PCR may give false-negative results in cases in which the CAG expansion is unusually long. We report a case of spinocerebellar ataxia type 2 (SCA2) in a 4-year-old girl with false-negative conventional PCR results. Specifically, the SCA2 disorder is caused by a CAG repeat within the ATXN2 gene on chromosome 12. Subsequent confirmatory testing using modified PCR and primers specific for the CAG repeat were performed and revealed an expanded allele with 109 repeats in our patient.

Preconceptual Risk Factors

Abstract: Identification of risk factors and anticipation of shoulder dystocia will help prevent fetal injury.

The Myotonic Dystrophies

Abstract: Myotonic dystrophy is a progressive, multi-systemic condition causing muscle weakness and myotonia. Additional symptoms include cataracts, gastrointestinal abnormalities, male reduced fertility, diabetes, and cardiac conduction defects. Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion in the DMPK gene and type 2 (DM2) by a CCTG repeat expansion in the ZNF9 gene. Whereas age of onset correlates with repeat size in DM1 with anticipation, onset and severity do not correlate well with the repeat expansion size in DM2. The non-dystrophic myotonic disorders produce myotonia without muscle weakness. These conditions are caused by mutations in ion channel genes.