Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
Add more filters










Publication year range
1.
Clin Genet ; 81(2): 128-41, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21496010

ABSTRACT

Despite a wide range of clinical tools, the etiology of mental retardation and multiple congenital malformations remains unknown for many patients. Array-based comparative genomic hybridization (aCGH) has proven to be a valuable tool in these cases, as its pangenomic coverage allows the identification of chromosomal aberrations that are undetectable by other genetic methods targeting specific genomic regions. Therefore, aCGH is increasingly used in clinical genetics, both in the postnatal and the prenatal settings. While the diagnostic yield in the postnatal population has been established at 10-12%, studies investigating fetuses have reported variable results. We used whole-genome aCGH to investigate fetuses presenting at least one major malformation detected on ultrasound, but for whom standard genetic analyses (including karyotype) failed to provide a diagnosis. We identified a clinically significant chromosomal aberration in 8.2% of tested fetuses (4/49), and a result of unclear clinical significance in 12.2% of tested fetuses (6/49). Our results document the value of whole-genome aCGH as a prenatal diagnostic tool and highlight the interpretation difficulties associated with copy number variations of unclear significance.


Subject(s)
Abnormalities, Multiple/genetics , Comparative Genomic Hybridization , DNA Copy Number Variations , Karyotype , Abnormalities, Multiple/diagnosis , Chromosome Aberrations , Fetus , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Prenatal Diagnosis , Reproducibility of Results
2.
Am J Med Genet ; 91(5): 383-6, 2000 Apr 24.
Article in English | MEDLINE | ID: mdl-10767003

ABSTRACT

We describe a child with a supernumerary chromosome defined as der(9)t(9;22) (q12;p11), resulting in trisomy 9p and trisomy 22p. The mother carried the balanced translocation. In G- and C-banding the derivative chromosome 9 appeared to be dicentric and to contain 22q material. Using in situ hybridization we defined the exact breakpoints of the translocation and ruled out the possibility of a centric fission in the mother's chromosomes.


Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 9 , Translocation, Genetic , Trisomy , Chromosome Banding , Female , Humans , Hypertelorism/genetics , In Situ Hybridization , Infant , Karyotyping , Microcephaly/genetics
3.
Am J Med Genet ; 87(4): 302-5, 1999 Dec 03.
Article in English | MEDLINE | ID: mdl-10588834

ABSTRACT

Duplication of a portion of Xq has been observed in males with abnormalities. In some cases, their mothers or even grandmothers had the same duplication but did not show any phenotypic abnormalities. However, a few cases of females with a de novo Xq duplication do present some abnormalities. We describe a 16-month-old girl with short stature, motor delay with hypotonia, scoliosis, right hemiatrophy, and ptosis of the right eye, with an Xq duplication. The duplicated region is read dir dup(X)(q22.1q25).


Subject(s)
Sex Chromosome Aberrations , X Chromosome/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Adult , Female , Growth Disorders/genetics , Growth Disorders/pathology , Humans , In Situ Hybridization, Fluorescence , Infant , Karyotyping , Male , Phenotype , Psychomotor Disorders/genetics , Psychomotor Disorders/pathology
4.
Am J Med Genet ; 82(2): 149-54, 1999 Jan 15.
Article in English | MEDLINE | ID: mdl-9934980

ABSTRACT

Prenatal diagnosis of chromosomal disorders has been performed for more than 20 years, mainly for advanced maternal age. Chromosomal abnormality rates derived from second trimester amniocentesis have mainly come from a collection of small-scale studies from North America and Western Europe. Accurate risk estimates for chromosomal abnormalities are important tools for the physician or obstetrician who would need to make referrals to a prenatal genetic center. This paper presents amniocentesis rates of clinically significant cytogenetic abnormalities for various indications, including advanced maternal age, previous chromosomal abnormality, parental structural rearrangement and a family history of aneuploidy as defined in the text. These data come from a Canadian prenatal diagnosis laboratory with more than 20 years experience in second trimester cytogenetic analysis. They show that the overall frequency of chromosomal abnormalities for advanced maternal age (> or = 35 years) is 1.79%. In this group, 21% of all abnormalities are structural rearrangements (including markers) and less than half of all abnormalities are trisomy 21. The advanced maternal age specific risk of aneuploidies at second trimester is 1.24%. Recurrence risk for aneuploidy after a previous one is 1.29%. However, it is much higher (4.84%) for women of > or = 35 years. When a parent's brother, sister, nephew or niece is affected, the risk of occurrence of aneuploidies (0.24%) is not elevated. When there is a balanced translocation in one of the parents, the overall risk is 10.2% for unbalanced translocations and 37.3% for balanced translocations.


Subject(s)
Amniocentesis , Chromosome Aberrations/epidemiology , Canada/epidemiology , Chromosome Disorders , Genetic Predisposition to Disease , Humans , Prenatal Diagnosis
5.
Cancer Genet Cytogenet ; 105(1): 14-9, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9689924

ABSTRACT

We report the cytogenetic and histopathological findings in a 7-year-old female child with an intranasal tumor that is most consistent with a parachordoma. Karyotypic analysis of the tumor revealed clonal numerical and structural chromosome abnormalities. Seven cells displayed recurrent changes: der(2)t(2;4), del(3q), and the loss of chromosomes 9, 10, 20, and 22. Four cells showed a loss of chromosome 17. To the best of our knowledge, these are the first clonal chromosome abnormalities described in parachordoma.


Subject(s)
Chordoma/genetics , Chromosome Aberrations/genetics , Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 3/genetics , Chromosomes, Human, Pair 4/genetics , Nose Neoplasms/genetics , Child , Chordoma/pathology , Chordoma/therapy , Chordoma/ultrastructure , Chromosome Disorders , Female , Flow Cytometry , Humans , Karyotyping , Microscopy, Electron , Nose Neoplasms/pathology , Nose Neoplasms/therapy , Nose Neoplasms/ultrastructure , Translocation, Genetic
6.
Cytogenet Cell Genet ; 75(1): 22-4, 1996.
Article in English | MEDLINE | ID: mdl-8995482

ABSTRACT

The chromosome locations of the rabbit (Oryctolagus cuniculus) Na+-phosphate cotransporter genes NPT1 and NPT2 were determined by fluorescence in situ hybridization. Our results localize NPT1 to rabbit chromosome 12p11 and NPT2 to rabbit chromosome 3p11. The corresponding genes in the human map to chromosome bands 6p22 and 5q35, respectively. These assignments agree with the previously reported homology between rabbit chromosome 12 and human chromosome 6 and provide the basis for the establishment of a conserved syntenic group between rabbit chromosome 3 and human chromosome 5.


Subject(s)
Carrier Proteins/genetics , Chromosome Mapping , Chromosomes, Human, Pair 5 , Chromosomes, Human, Pair 6 , Symporters , Animals , Chromosome Banding , Humans , In Situ Hybridization, Fluorescence , Rabbits , Sodium-Phosphate Cotransporter Proteins , Sodium-Phosphate Cotransporter Proteins, Type I , Sodium-Phosphate Cotransporter Proteins, Type III
7.
Cytogenet Cell Genet ; 72(1): 9-11, 1996.
Article in English | MEDLINE | ID: mdl-8565644

ABSTRACT

The chromosomal localization of the gene for retinoblastoma (RB1), which has been mapped to band 13q14 in man, was studied by in situ hybridization on metaphase chromosomes of selected primates, including Pithecia pithecia, Macaca sylvana, and Cercopithecus aethiops tantalus. The results allowed us to determine the position of the bands homologous to human chromosome band 13q14 in these species. Hybridization analysis corroborated the results of previous studies that defined the chromosome homologous to human chromosome 13 (HSA 13) in these species. By comparing RB1 localizations and banding patterns, it is shown that the rearrangement separating HSA 13 from its homologous chromosome in Cercopithecidae is not a pericentric inversion, as suggested by earlier studies. Since the banding pattern and RB1 localization are not changed, the modification of the centromeric index is explained by a centromeric shift or by two inversions, one pericentric and one paracentric.


Subject(s)
Cebidae/genetics , Cercopithecus/genetics , Haplorhini/genetics , Macaca/genetics , Retinoblastoma Protein/genetics , Animals , Chromosome Mapping , Chromosomes, Human, Pair 13 , Humans , In Situ Hybridization, Fluorescence
8.
Hum Genet ; 93(5): 563-7, 1994 May.
Article in English | MEDLINE | ID: mdl-8168835

ABSTRACT

A girl with severe Becker muscular dystrophy and apparently normal chromosomes had a heterozygous deletion for exons 51, 52, and 53 of the dystrophin gene. This deletion was transmitted by her mother, who was unaffected. To differentiate the normal and the deleted X chromosomes, fluorescence in situ hybridization (FISH) was applied to metaphase chromosomes, using probes for both exons 51 and 52, which are only 388 and 113 base pairs long, respectively. FISH signals were observed in one or both chromatids of one chromosome, but never on both chromosomes, suggesting the lack of hybridization on the deleted X chromosome. Using 5-bromodeoxyuridine incorporation to differentiate the late (inactive) and the early replicating (active) X chromosomes, 77% of the signals were observed on the active X chromosomes in the mother. This percentage was only 18% in the daughter, suggesting that skewed inactivation of the X chromosomes was responsible for the phenotypic differences.


Subject(s)
Chromosome Deletion , Dosage Compensation, Genetic , Dystrophin/genetics , Muscular Dystrophies/genetics , Sex Chromosome Aberrations/genetics , X Chromosome , Adolescent , Adult , Blotting, Western , Cytogenetics , DNA/analysis , Dystrophin/metabolism , Exons/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Muscles/metabolism , Muscular Dystrophies/metabolism , Phenotype
10.
J Bone Miner Res ; 8(11): 1397-406, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8266831

ABSTRACT

We have cloned part of the human 25-OHD 24-hydroxylase cytochrome P450 (P450cc24) cDNA. The characterized sequence consists of 776 bp of the coding and 720 bp of the 3'-untranslated region interrupted by an intron. In the coding region we found 79.8% similarity in DNA and 87.5% in deduced amino acid sequences between human and rat, with no similarity in the 3'-untranslated region. By Southern blot hybridization of DNA from human-hamster somatic cell hybrids and by in situ immunofluorescence hybridization, we mapped P450cc24 to human chromosome 20q13.1. This location of P450cc24 is different from that of pseudovitamin D-deficient rickets (PDDR), previously assigned to chromosome 12q14 by linkage analysis, thus excluding it as a target of the PDDR mutation. Since it is likely that PDDR is caused by a mutation in the 25-OHD 1 alpha-hydroxylase P450 subunit (P450cc1 alpha) our results do not support the hypothesis that the two cytochromes are encoded by a single gene.


Subject(s)
Chromosome Mapping , Cytochrome P-450 Enzyme System/genetics , Steroid Hydroxylases/genetics , Vitamin D Deficiency/genetics , Amino Acid Sequence , Animals , Base Sequence , Cricetinae , Humans , Molecular Sequence Data , Rats , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Vitamin D Deficiency/enzymology , Vitamin D3 24-Hydroxylase
12.
Genes Dev ; 6(8): 1373-85, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1644285

ABSTRACT

Over 1000 nucleotides may separate the ribozyme core of some group I introns from their 3' splice junctions. Using the sunY intron of bacteriophage T4 as a model system, we have investigated the mechanisms by which proximal splicing events are suppressed in vitro, as well as in vivo. Exon ligation as well as cleavage at the 5' splice site are shown to require long-range pairing between one of the peripheral components of the ribozyme core and some of the nucleotides preceding the authentic 3' splice junction. Consistent with our three-dimensional modeling of the entire sunY ribozyme, we propose that this novel interaction is necessary to drive 5' exon-core transcripts into an active conformation. A requirement for additional stabilizing interactions, either RNA-based or mediated by proteins, appears to be a general feature of group I self-splicing. A role for these interactions in mediating putative alternative splicing events is discussed.


Subject(s)
Genes, Viral/genetics , Introns/physiology , RNA Splicing/genetics , RNA, Catalytic/metabolism , RNA, Messenger/metabolism , Base Sequence , DNA Mutational Analysis , Escherichia coli/genetics , Introns/genetics , Magnesium/metabolism , Molecular Sequence Data , Mutation/genetics , Nucleic Acid Conformation , Plasmids/genetics , RNA, Catalytic/genetics , RNA, Messenger/genetics , T-Phages/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...