No abstract availble.
Adenoma/diagnosis/epidemiology/*etiology ; Anticipation, Genetic ; Colonic Neoplasms/diagnosis/epidemiology/*etiology ; Humans ; *Insulin Resistance ; Obesity/*complications/epidemiology ; Risk Factors

Dentatorubro-pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder with various clinical phenotypes and has a cytosine-adenine-guanine (CAG) trinucleotide repeat in a gene on chromosome 12. It has been known that trinucleotide repeat disorders show strong inverse correlations between the CAG repeat number and the age of onset and genetic anticipation. The purpose of this study was to investigate whether these observations are applicable to Korean patients. This report involved three Korean families and had on file the history of the 15 affected family mem-bers .Seven of the affected members had the diagnosis of DRPLA which was confirmed by a gene study. We observed inverse correlations between the CAG repeat number and the age of onset and genetic anticipation with high intra- and interfamilial variations. Although our study was in general agreement with previously documented features of DRPLA, some features could not be explained by currently understood pathophysiologic mechanisms.
Age of Onset ; Anticipation, Genetic ; Atrophy* ; Chromosomes, Human, Pair 12 ; Diagnosis ; Genes, vif ; Humans ; Molecular Biology* ; Neurodegenerative Diseases ; Phenotype ; Trinucleotide Repeats

BACKGROUND: Myotonic dystrophy is the most common type of muscular dystrophy affecting adults, associated with the expansion of triplet repeat DNA sequences. A hallmark of the inherited disease with trinucleotide repeat DNA expansion is the clinical and genetic anticipation. The copy numbers of the CTG repeat are known to be related to the severity and the onset age of clinical symptoms. METHODS: The copy numbers of the CTG repeats were determined using PCR amplification and Southern blotting. The clinical manisfestations of 34 patients from 14 families who had the CTG repeat expansion were evaluated based on the muscular disability rating scale and the electrophysiological study. RESULTS: There was a significant positive correlation between the clinical scores and the size of the amplification of trinucleotide repeat, and a negative correlation with the age of onset. In 9 patients with copy numbers of CTG repeats between 61 and 100, 8 cases were asymptomatic and myotonic discharges were not seen in 71% of patients. Larger expanded bands, earlier onset, and worse symptoms were evident with each successive generation. CONCLUSIONS: Molecular genetic analysis with CTG repeat expansion might be useful in the detection and the genetic counseling of myotonic dystrophy patients.
Adult ; Age of Onset ; Anticipation, Genetic ; Base Sequence ; Blotting, Southern ; DNA ; Genetic Counseling ; Humans ; Molecular Biology ; Muscular Dystrophies ; Myotonic Dystrophy* ; Polymerase Chain Reaction ; Trinucleotide Repeats

OBJECTIVES: The genetic facotrs have been suggested for the etiology of mood disorders but the mode of inheritance is complex. Increased severity and an earlier onset of the bipolar and major depressive disorder over generations within families(Anticipation) were reported. In order to test the hypothesis that trinucleotide repeat expansions underlie the genetic basis of Bipolar and major depressive disorders, we have analyzed the extent of CAG reapeats in genomic DNA from mood disorder patients. METHODS: 55 bipolar disorder, 67 major depressive disorder patients were recruited according to the DSM-III-R criteria. 89 normal controls were recruited from the medical personnel, students and the visitors to the health services center who had no history of psychiatric illness and show normal profile of MMPI. The genomic DNA of patients and controls was analyzed by use of the(CTG) 17 oligonucleotide and the repeat expansion detection(RED) method. The Mann-Whitney U test was used to compare the distribution of the number of CAG repeats among the groups. RESULTS: when the bipolar disorder, major depressive disorder patients were compared with the control group, no significant differences were observed. CONCLUSION: Our results do not support the hypothesis that expanding CAG repeats are causing the observed genetic anticipation in bipolar disorders and major depressive disorders.
Anticipation, Genetic ; Bipolar Disorder ; Depressive Disorder, Major ; DNA ; Family Characteristics ; Health Services ; Humans ; MMPI ; Mood Disorders* ; Trinucleotide Repeat Expansion ; Trinucleotide Repeats ; Wills

OBJECTIVETo analyze the SPG3A coding sequence and clinical features in a family with dominantly inherited hereditary spastin paraplegia (HSP) characterized by incomplete genetic penetrance and genetic anticipation.

METHODSAnalysis of the SPG3A coding sequence, being sequence variations in SPG4/spastin (S44L and P45Q) and SPG6/nipa1([GCG]5-11) genes were performed for the proband, his affected son, his unaffected parents and unaffected brother. One hundred normal individuals were selected as controls.

RESULTSSPG3A mutation V253I in the proband, his affected son, and unexpectedly, in his asymptomatic, 72 year old father was identified. No mutation at the same site was found in the other members of this family as well as the control.

CONCLUSIONIncomplete genetic penetrance due to SPG3A mutation V253I was observed in this family. This is the second report. Marked phenotype variation (genetic non-penetrance, adult versus childhood onset symptoms) between subjects with the same SPG3A mutation indicates the influence of modifying genetic or environmental factors. Progressively earlier symptom onset and increasing symptom severity in this family is consistent with genetic anticipation which has not been previously reported in SPG3A-HSP.

Aged ; Aged, 80 and over ; Anticipation, Genetic ; Base Sequence ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; GTP Phosphohydrolases ; genetics ; GTP-Binding Proteins ; Humans ; Male ; Membrane Proteins ; Middle Aged ; Pedigree ; Penetrance ; Polymerase Chain Reaction ; Spastic Paraplegia, Hereditary ; genetics