1/31. Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid.OBJECTIVES: The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM). BACKGROUND: Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. methods: Clinical and genetic analysis of the family was carried out. RESULTS: echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS: This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial dna defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients.- - - - - - - - - - ranking = 1keywords = acid (Clic here for more details about this article) |
2/31. Early onset of X-linked Emery-Dreifuss muscular dystrophy in a boy with emerin gene deletion.A boy developed contractures of the Achilles tendons at 3 years and of the postcervical muscles at 7 years, although neither contractures of the elbows nor cardiac abnormality were recognized by the age of 9 years. Muscle computed tomography scanning revealed changes characteristic of muscle involvement. Emerin was not detected in the biopsied muscle, and RT-PCR and PCR-based genomic dna analyses of the emerin gene demonstrated no amplification product in the patient. These results confirmed the diagnosis of X-linked Emery-Dreifuss muscular dystrophy (EDMD), and reinforce the necessity of molecular genetic diagnosis of the membrane protein emerin in younger patients with possible EDMD before appearance of the typical symptoms, to avoid sudden cardiac death.- - - - - - - - - - ranking = 329.55523215638keywords = amplification (Clic here for more details about this article) |
3/31. frasier syndrome: a cause of focal segmental glomerulosclerosis in a 46,XX female.The description of frasier syndrome until now has been restricted to XY females with gonadal dysgenesis, progressive glomerulopathy, and a significant risk of gonadoblastoma. Mutations in the donor splice site in intron 9 of the Wilms' tumor (WT1) gene have been shown to cause frasier syndrome and are distinct from WT1 exon mutations associated with denys-drash syndrome. The WT1 gene, which is essential for normal kidney and gonadal development, encodes a zinc finger transcription factor. The intron 9 alternative splice donor site mutation seen in frasier syndrome leads to loss of three amino acids ( KTS isoform), thus disrupting the normal ratio of the KTS/-KTS isoforms critical for proper gonadal and renal development. This study examines two sisters with identical intron 9 mutations. The proband carries a classic diagnosis of frasier syndrome with 46,XY gonadal dysgenesis, whereas her sister has progressive glomerulopathy but a 46,XX karyotype and normal female development. This indicates that the proper WT1 isoform ratio is critical for renal and testicular development, but apparently does not affect either ovarian development or function. It is proposed that the clinical definition of frasier syndrome should be broadened to include 46,XX females with normal genital development and focal segmental glomerulosclerosis associated with a WT1 intron 9 donor splice site mutation. Nephrologists need to consider the possibility of this heritable syndrome in evaluation of females with focal segmental glomerulosclerosis and to consider their risk for gonadal malignancy, as well as the risk for kidney disease, gonadal dysgenesis, and malignancy in their offspring.- - - - - - - - - - ranking = 0.16666666666667keywords = acid (Clic here for more details about this article) |
4/31. Structural X-chromosome abnormality in a female with gonadal dysgenesis.A patient with gonadal dysgenesis and 46 chromosomes is described. In the inactive x chromosome there seems to be a deletion of the short arms and an insertion of heterochromatin in the long arms. The most probable mechanism to explain this structurally abnormal X is a pericentric inversion, with breakage and union having occurred in the centromeric heterochromatin of the short arm and in band q23 of the long arm. An amplification of the centromeric heterochromatin left in the short arm is also supposed.- - - - - - - - - - ranking = 329.55523215638keywords = amplification (Clic here for more details about this article) |
5/31. prenatal diagnosis of two rare de novo structural aberrations of the y chromosome: cytogenetic and molecular analysis.Two rare de novo structural aberrations of the y chromosome were detected during routine prenatal diagnosis: a satellited non-fluorescent y chromosome (Yqs), the first de novo Yqs to be reported in a fetus, and a terminal deletion of the y chromosome long arm del(Y)(q11). In both cases detailed cytogenetic and molecular analyses were undertaken. In the case of the Yqs it was demonstrated by fluorescence in situ hybridization (FISH) that the satellites were derived from chromosome 15. In the case of the del(Yq), it was shown with molecular analysis by polymerase chain reaction (PCR) amplification of sequence-tagged sites (STS-PCR) that the deleted portion of the long arm of chromosome Y included the azoospermia factor loci, AZFb and AZFc. The clinical significance of these findings is discussed.- - - - - - - - - - ranking = 329.55523215638keywords = amplification (Clic here for more details about this article) |
6/31. Characterisation of two mutations in the ABCD1 gene leading to low levels of normal ALDP.A variety of mutations have been identified in the X-linked adrenoleukodystrophy (X-ALD) gene, none of which is prevalent. In this work we describe a reverse transcription polymerase chain reaction (RT-PCR)-based strategy specially suited to the molecular characterisation of mutations in index cases. After RT-PCR amplification of the X-ALD transcript a conformation-sensitive gel electrophoresis analysis is performed followed by sequencing of the fragments with altered mobility. Two X-ALD patients were studied using this strategy. In both cases, splice site mutations were found. The first patient studied has a single base substitution at the first position of the invariant GT dinucleotide donor splice site of intron 8. In spite of this alteration, small quantities of correctly spliced mRNA molecules were easily detected. In agreement with these data, a small amount of ALDP was found by western blotting analysis. An alteration at the -1 position of the donor splice site of exon 1 was detected in the second patient. This mutation results in the utilisation of a cryptic 5' splice site within intron 1. Nevertheless, this transition also allows for some correct splicing. Western blotting analysis revealed the existence of normal-migrating ALDP. However, as expected, the levels of this protein were greatly decreased. Taken together, our data suggest that some less severe or late-onset forms of X-ALD associated with splice mutations result from the production of small amounts of normal ALDP. It is proposed that the quantification of ALDP levels in these patients could provide important insights concerning the correlation between clinical phenotype and amount of normal ALDP.- - - - - - - - - - ranking = 329.55523215638keywords = amplification (Clic here for more details about this article) |
7/31. 47,XX mar karyotype containing genes from the azoospermia factor region. A case report.BACKGROUND: Abnormal embryo development is the major cause of implantation failure and accounts for the low rate of human fertility in vitro and in vivo. Chromosome abnormalities are widely involved in this process through meiotic nondisjunction, fertilization abnormalities and mitotic nondisjunction. CASE: In our assisted reproductive technology program a couple underwent cytogenetic analysis. The woman had a 47,XX mar karyotype. We investigated this patient by chromosome analysis, fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) dna analysis. The marker chromosome was found to be very similar to a y chromosome in size and QFQ staining pattern. Therefore, it was tested by FISH using alpha- and beta-satellite dna specific for the y chromosome, some YACs specific for the long arm of the y chromosome and alpha-satellite dna specific for 15 chromosomes as probes. In order to define this marker, the next step was PCR amplification of the whole genomic dna using specific landmarks (sequence-tagged sites) to encompass the azoospermia factor (AZF) region on the long arm of the y chromosome. CONCLUSION: A woman had an extra chromosome containing centromeric dna derived from the Y and 15 other chromosomes, heterochromatic regions derived from 15 chromosomes and a large heterochromatic block at the end of the long arm that definitely was not y chromosome heterochromatin (beta-satellite). PCR showed several genes of the y chromosome long arm that are assumed to be involved in male gametogenesis. Phenotypic effects could not be excluded because of the presence of AZF genes. Oocyte karyotyping might better explain the role of the genetic problem on female infertility.- - - - - - - - - - ranking = 329.55523215638keywords = amplification (Clic here for more details about this article) |
8/31. First clinical application of comparative genomic hybridization and polar body testing for preimplantation genetic diagnosis of aneuploidy.OBJECTIVE: To develop a preimplantation genetic diagnosis (PGD) protocol that allows any form of chromosome imbalance to be detected.DESIGN: Case report employing a method based on whole-genome amplification and comparative genomic hybridization (CGH).SETTING: Clinical IVF laboratory.PATIENT(S): A 40-year-old IVF patient.INTERVENTION(S): Polar body and blastomere biopsy.MAIN OUTCOME MEASURE(S): Detection of aneuploidy.RESULT(S): Chromosome imbalance was detected in 9 of 10 polar bodies. A variety of chromosomes were aneuploid, but chromosomal size was found to be an important predisposing factor. In three cases, the resulting embryos could be tested using fluorescence in situ hybridization, and in each case the CGH diagnosis was confirmed. A single embryo could be recommended for transfer on the basis of the CGH data, but no pregnancy ensued.CONCLUSION(S): Evidence suggests that preferential transfer of chromosomally normal embryos can improve IVF outcomes. However, current PGD protocols do not allow analysis of every chromosome, and therefore a proportion of abnormal embryos remains undetected. We describe a method that allows every chromosome to be assessed in polar bodies and oocytes. The technique was accurate and allowed identification of aneuploid embryos that would have been diagnosed as normal by standard PGD techniques. As well as comprehensive cytogenetic analysis, this protocol permits simultaneous testing for multiple single-gene disorders.- - - - - - - - - - ranking = 329.55523215638keywords = amplification (Clic here for more details about this article) |
9/31. Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of Xp.The microphthalmia with linear skin defects syndrome (MLS) is an X-linked dominant disorder with male lethality. In the majority of the patients reported, the MLS syndrome is caused by segmental monosomy of the Xp22.3 region. To date, five male patients with MLS and 46,XX karyotype ("XX males") have been described. Here we report on the first male case with MLS and an XY complement. The patient showed agenesis of the corpus callosum, histiocytoid cardiomyopathy, and lactic acidosis but no microphthalmia, and carried a mosaic subtle inversion of the short arm of the x chromosome in 15% of his peripheral blood lymphocytes, 46,Y,inv(X)(p22.13 approximately 22.2p22.32 approximately 22.33)[49]/46,XY[271]. By fluorescence in situ hybridization (FISH), we showed that YAC 225H10 spans the breakpoint in Xp22.3. End-sequencing and database analysis revealed a YAC insert of at least 416 kb containing the genes HCCS and AMELX, and exons 2-16 of ARHGAP6. Molecular cytogenetic data suggest that the Xp22.3 inversion breakpoint is located in intron 1 of ARHGAP6, the gene encoding the Rho GTPase activating protein 6. Future molecular studies in karyotypically normal female MLS patients to detect submicroscopic rearrangements including the ARHGAP6 gene as well as mutation screening of ARHGAP6 in patients with no obvious chromosomal rearrangements will clarify the role of this gene in MLS syndrome.- - - - - - - - - - ranking = 0.16666666666667keywords = acid (Clic here for more details about this article) |
10/31. sex chromosome rearrangements leading to partial aneuploidies and mosaicisms: use of QF-PCR for detection and quantification of the involved cell lines.Chromosome rearrangements can lead to aneuploidies of specific chromosome regions and could be present in the entire individual or limited to some tissues (mosaicism) depending on the developmental stage of the embryo when the rearrangement occurs. We report 6 cases with sex chromosome rearrangements identified by conventional cytogenetics and tested by quantitative fluorescent polymerase chain reaction (QF-PCR). QF-PCR has been largely employed for rapid detection of common aneuploidies in pre-natal and post-natal diagnosis and consists in dna amplification by polymerase chain reaction (PCR) using fluorescent labelled primers and the analysis of chromosome specific small tandem repeats (STR). We tested 5 sex chromosome specific STR markers in multiplex PCR amplifications together with other chromosome specific STR markers as control amplifications. The PCR products were analysed by capillary electrophoresis. The results from QF-PCR analysis were obtained within one day and confirmed our cytogenetic observations. This study shows that QF-PCR analysis can detect sex chromosome imbalance and also suspect mosaicism or chromosome rearrangement.- - - - - - - - - - ranking = 988.66569646915keywords = amplification (Clic here for more details about this article) |
| | Next -> |