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Molecular Genetic Study (molecular + genetic_study)
Selected AbstractsMolecular Genetic Study on Angelman Syndrome Patients without a Chromosomal DeletionEPILEPSIA, Issue 2000Shinji Saitoh Purpose: Angelman syndrome (AS) is a ncurobehavioral disorder characterized by severe mental retardation, easily cvoked laughter, ataxic gait, and epilepsy. Epilepsy associated with AS is characterized by early childhood onset gencralized seizures with profound EEG abnormalities. Therefore, AS is a good human model for genetic epilepsy syndromes. Approximately 70% of AS cases are caused by maternal deletions of chromosomc 15q I I-qI3; whereas, 30% are not associated with a chromosomal dcletion. Thcse non-deletion AS patients are caused by paternal uniparental disomy (UPD), imprinting mutation (IM), or loss-or-function mutations of the UBE3A gene, cach of which predisposes different recurrence risk. To elucidate molecular etiology of non-dclction AS patients, we investigated 34 AS patients without a chromosomal deletion. Methods: Thirty sporadic AS patients, and 4 familial AS patients (2 families of 2 sibs) were enrolled to the study. The diagnosis of AS was based on Williams' criteria (Williams et al., Am J Med Genet 1995, 56: 237). Genomic DNA was extracted from peripheral blood by a standard procedure. DNA mcthylation tcst at SNRPN locus and genotyping using 7 highly informative PCR-based polymorphisms within 15q I I - q I3 were carried out to identify UPD and IM. When both UPD and IM were ruled out, the patients were classified :LS non-UPD, non-IM. For thcsc non-UPD, non-1M paticnts, UBE3A mutations were screened by PCR-SSCP analysis using 10 sets ofprimcrs covering all coding exons. Results: Among 30 sporadic patients, I UPD and 3 IM patients were identified, and the remaining 26 patients were classified as non-UPD, non-IM. Among 4 familial patients, 2 sibs from I family were detected as IM, whcrcas 2 sibs from another family were classified as non-UPD, non-IM. No UBE3A mutations were identified within 26 sporadic and 2 familial non-UPD, non-IM patients. Conclusion: Threc molecular classes were identified for noindeletion AS patients. Therefore, the underlying genetic mechanism was dcmonstratcd to be complex for AS patients without a chromosomal deletion. Combination of the DNA methylation test and PCR-based polymorphisms was sufficient to detect UPD and IM patients. Because recurrence risk is low for UPD and high lor IM, systematic molecular investigation including the DNA methylation test and PCR-based polymorphisms should bc donc for non-delction AS paticnts for genetic counscling purpose. A majority of non-deletion patients were classified as noii-UPD, non-1M. Although, approximate 30% of non-UPD, nonIM patients arc rcportcd to have UBE3A mutations, no such mutations were identified in our study. An underlying molecular mechanism was not rcvealcd for this group of patients, and therefore, assessment of recurrence risk was difficult. Further investigation is necessary for noii-UPD, non-1M paticnts. [source] Molecular genetic study of congenital nephrogenic diabetes insipidus and rescue of mutant vasopressin V2 receptor by chemical chaperonesNEPHROLOGY, Issue 2 2007HAE IL CHEONG SUMMARY: Aim: X-linked nephrogenic diabetes insipidus is a rare disease caused by mutations in the arginine vasopressin V2 receptor (AVPR2) gene, which encodes vasopressin V2 receptor (V2R). More than a half of reported mutations in AVPR2 are missense mutations, and a large number of missense mutant receptors fail to fold properly and therefore are not routed to the cell surface. Methods: We analysed the AVPR2 gene in 14 unrelated patients with X-linked nephrogenic diabetes insipidus, and found 13 different mutations including eight missense point mutations. The cellular expression patterns of three missense mutant (A98P, L274P and R113W) and wild-type V2R were determined in transfected COS-7 cells. Results: In contrast to wild-type V2R, the cell-surface expressions of mutant receptors were totally (A98P and L274P) or partially (R113W) absent. Instead, they were retained intracellularly. However, treatment of cells with two chemical chaperones (100 mmol/L trimethylamine oxide or 2% dimethyl sulfoxide) or incubation at 26°C restored the cell-surface expressions of mutant receptors. Conclusion: These data show that some chemical chaperones correct the mistrafficking of misfolded A98P, L274P and R113W V2R. Thus, we believe that a therapeutic strategy based on chemical chaperones in patients with these mutations is worth trying. [source] Prenatal Marfan syndrome: report of one case and review of the literaturePRENATAL DIAGNOSIS, Issue 8 2006K. R. M. Lopes Abstract Objectives Our objective was to describe the features of prenatal Marfan syndrome. Methods Doppler fetal echocardiograms were performed. The morphology and rhythm of the fetal heart were examined sequentially. Results The case was referred because of cardiomegaly and dilated great vessels. Sequential Doppler echocardiographic evaluation led to the diagnosis of prenatal Marfan syndrome. The main features are cardiomegaly, dysplastic atrioventricular valves with tricuspid regurgitation and dilated great vessels, which can be aneurysmal at their origin. The fetus died in utero at 39 weeks of gestation because of cardiac failure. Pathological study confirmed the Marfan habitus and complications. Molecular genetic study showed a de novo point mutation in exon 26 of the FBN1 gene. Conclusion We report a case of prenatal Marfan syndrome diagnosed by sequential evaluation of the cardiac signs, which are essential for prenatal diagnosis. The prognosis seems as poor as the neonatal one. The prenatal diagnosis is essential for adequate counselling. Copyright © 2006 John Wiley & Sons, Ltd. [source] A further case of confined placental mosaicism for trisomy 2 associated with adverse pregnancy outcomePRENATAL DIAGNOSIS, Issue 7 2003Eileen Roberts Abstract Objectives To add to the knowledge base concerning confined placental mosaicism for trisomy 2. Methods Cytogenetic study of a late CVS referred for hyperechogenic bowel and raised AFP, and cytogenetic and molecular genetic study of a follow-up amniocentesis. Ultrasound monitoring at regular intervals following the CVS result. Results All cells examined from direct and cultured CVS showed a 47,XY,+2 karyotype. Amniocentesis showed a mosaic 47,XY,+2[8]/46,XY[81] karyotype. Uniparental disomy (UPD) studies on the amniotic fluid showed normal biparental inheritance. The pregnancy developed oligohydramnios and IUGR and resulted in a 26-week liveborn male infant with a 46,XY karyotype, which died after 3 days because of complications of severe prematurity. Placental villi post delivery showed only the 47,XY,+2 cell line. Conclusions This case represents a further example of confined placental mosaicism (CPM) for trisomy 2 associated with oligohydramnios, IUGR and poor pregnancy outcome. Copyright © 2003 John Wiley & Sons, Ltd. [source] Genetic structure in ixodid ticks from Kangaroo Island and the South Australia mainlandAUSTRALIAN JOURNAL OF ENTOMOLOGY, Issue 1 2009Thomas W Chapman Abstract We describe here a molecular genetic study designed to elucidate the ability of an ixodid tick to move within their range as well as between species or hosts. A direct match from the contiguous regions of the small rRNA subunit, control region #1, tRNA-Ile, tRNA-Gln and tRNA-Met of the population studied here with previously published sequence suggests that the species is likely Ixodes hirsti. Phylogenetic analysis of tick haplotypes showed no evidence for bird-host specialisation, and a nested clade analysis indicated a high degree of migration between our three collection sites (two sites on Kangaroo Island, and one site on mainland South Australia). [source] | |||||||||||||