A putative susceptibility locus on chromosome 18 is not a major contributor to human selective IgA deficiency: evidence from meiotic mapping of 83 multiple-case families.
(25/992)
Previous reports of an association between constitutional chromosome 18 abnormalities and low levels of IgA suggested that this chromosome contains a susceptibility locus for selective IgA deficiency (IgAD), the most frequent Ig deficiency in humans. IgAD is genetically related to common variable immunodeficiency (CVID), characterized by a lack of additional isotypes. Our previous linkage analysis of 83 multiple-case IgAD/CVID families containing 449 informative pedigree members showed a significantly increased allele sharing in the chromosome region 6p21 consistent with allelic associations in family-based and case-control studies and provided the evidence for a predisposing locus, termed IGAD1, in the proximal part of the MHC. We have typed the same family material at 17 chromosome 18 marker loci with the average intermarker distance of 7 cM. A total of 7633 genotypes were analyzed in a nonparametric linkage analysis, but none of the marker loci exhibited a significantly increased allele sharing in affected family members. In addition, reverse painting and deletion mapping of a panel of constitutional chromosome 18 deletions/translocations showed the presence of IgA-deficient and IgA-proficient patients with the same abnormality and did not reveal a region commonly deleted. The linkage analysis of chromosome 8 and 21 regions involved in reciprocal translocations t(8;18) and t(18;21), which were identified in two patients lacking IgA, did not disclose a significant allele sharing. Although these results do not exclude the presence of a minor predisposing locus on this chromosome, such a putative locus would confer a population risk of developing IgAD/CVID much lower than IGAD1. (+info)
Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter.
(26/992)
We have identified a novel developmental disorder with complex phenotypic characteristics involving primarily the nervous system, which appears to be common in a specific Gypsy group in Bulgaria. We propose to refer to the syndrome as congenital cataracts facial dysmorphism neuropathy (CCFDN). We have assigned the disease locus to the telomeric region of chromosome 18q. Linkage disequilibrium and highly conserved haplotypes suggest genetic homogeneity and founder effect. CCFDN co-localises with an EST which shows high homology to a conserved Drosophila gene involved in the regulation of nervous system development in vertebrates. (+info)
Primary torsion dystonia: the search for genes is not over.
(27/992)
A GAG deletion in the DYT1 gene accounts for most early, limb onset primary torsion dystonia (PTD). The genetic bases for the more common adult onset and focal PTD are less well delineated. Genetic loci for an "intermediate dystonia" phenotype and for torticollis, named DYT6 and DYT7 respectively, have recently been mapped in single families. To evaluate the contribution of these genetic loci to other families with familial "non-DYT1" dystonia five large families with dystonia were studied using genetic markers spanning the DYT6 and DYT7 regions. There was no evidence of linkage to either locus in any family. These findings illustrate the genetic heterogeneity of the dystonias and indicate the existence of one or more as yet unmapped genes for dystonia. Large collaborative efforts will be required to identify these, and additional genes, causing PTD. (+info)
Primary pericardial synovial sarcoma with detection of the chimeric transcript SYT-SSX.
(28/992)
We report a case of a 19-year-old woman with a primary pericardial synovial sarcoma that extended from the right ventricular free wall to the posterior aspect of the left anterior thoracic wall. Synovial sarcoma was diagnosed by the detection of the chimeric transcript SYT-SSX using reverse transcriptase-polymerase chain reaction (RT-PCR). This transcript is generated by reciprocal translocation between chromosomes X and 18, and is specific to synovial sarcoma that usually occurs in the extremities of young adults. When pathological and immunohistochemical diagnosis of synovial sarcoma is difficult, the molecular biological technique using RT-PCR becomes a powerful method of confirmation of this neoplasm. (+info)
Trisomy 18 in Kuwait.
(29/992)
BACKGROUND: Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS: Ascertainment of T18 cases was performed shortly after birth. Chromosomal studies were carried out in addition to other relevant investigations. To investigate the factors associated with T18, a case-control study was carried out with 131 normal healthy newborns. Studied factors included maternal and paternal age, birth order, abortion, associated malformation, and survival. Multiple logistic regression analysis was used to adjust for confounding between variables. RESULTS: There was a preponderance of females among T18 cases (female:male ratio 2.1:1). The majority of T18 cases (53%) died before the second week of life. The most common associated anomalies were: congenital heart (38.1%) and gastrointestinal (25.4%). Multiplicity of malformations was also observed. Significant seasonal variation in T18 cases was detected with a peak in spring. Of the 118 T18 cases, 59 were delivered during 1994-1997 (average overall T18 birth prevalence rate 8.95 per 10 000 live births [95% CI: 6.66-11.23]). Concerning maternal age, 30.5% of the T18 cases' mothers were > or =35 years compared to 10.7% in the control group. The difference was statistically significant, P = 0.002. Logistic regression analysis showed that maternal age >30 years was a significant risk factor for T18, after adjusting for confounding with paternal age. Paternal age and abortion were not found to be significant risk factors. CONCLUSION: Trisomy 18 birth prevalence rate is high in Kuwait with advanced maternal age as a significant risk factor. (+info)
Role of multicolor fluorescence in situ hybridization (FISH) in simultaneous detection of probe sets for chromosome 18, X and Y in uncultured amniotic fluid cells.
(30/992)
Major aneuploidies diagnosed prenatally involve the autosomes 13, 18, and 21, and sex chromosomes. Fluorescence in situ hybridization (FISH) allows rapid analysis of chromosome copy number in interphase cells. The purpose of this study was to evaluate the role of multicolor fluorescence in situ hybridization in simultaneous detection of probe sets for chromosome 18, X, and Y in uncultured amniotic fluid cells as a safer alternative method for aneuploidy detection prenatally. Fifty amniotic fluid samples were analyzed by FISH and standard cytogenetics. Mean time to obtain results was three days for fluorescence in situ hybridization and 20 days for karyotype. Fluorescence in situ hybridization was informative in 43 samples (86%), and within this group, two aneuploidies were correctly identified. This evaluation demonstrates that FISH with X, Y, and 18 alpha satellite DNA probes could accurately and rapidly detect aneuploidies involving these chromosomes and could be used in any prenatal clinical laboratory. (+info)
Transmission/disequilibrium tests for extended marker haplotypes.
(31/992)
A generalization of the transmission/disequilibrium test to detect association between polymorphic markers and discrete or quantitative traits is discussed, with particular emphasis on marker haplotypes formed by several adjacent loci. Furthermore, strategies for testing haplotype association, using methods from spatial statistics, are developed. This approach compares the "similarity" of transmitted and untransmitted haplotypes, with the aim of determining the regions where there is greater similarity within the transmitted set. This arises from the fact that, although the original haplotypes carrying the mutation will be broken down by recombination, there may be a subset of markers near the mutation that are common to many of the recombinant haplotypes. Thus, by examination of each marker in turn and by measurement of the average size of the region shared identically by state in the transmitted and untransmitted haplotypes, it may be possible to detect regions of linkage disequilibrium that encompass the susceptibility gene. (+info)
High-dose therapy supported with immunomagnetic purged autologous bone marrow in high-grade B cell non-Hodgkin's lymphoma.
(32/992)
From August 1987 to March 1995, 25 patients with high-grade B cell non-Hodgkin's lymphoma (NHL) were treated with high-dose therapy (HDT) followed by bone marrow purged with immunomagnetic beads. At the time of transplantation, 20 patients were in sensitive relapse and five in first complete or partial remission. Ten patients had secondary high-grade NHL transformed from low-grade NHL. The HDT consisted of TBI followed by high-dose cyclophosphamide. All patients engrafted, except for two patients with early treatment-related death. Eleven patients relapsed, of whom nine died of lymphoma, and two are alive in new CR. The estimated event-free and overall survivals at 5 years were 40% and 48%, respectively, with a median follow-up of 48 months (range 1-123). Eight of the tumours contained the translocation t(14;18) at the major breakpoint region (MBR) of BCL-2. In these patients the presence of tumour cells in the bone marrow graft before and after purging were assessed by PCR. Four of five patients infused with non-detectable minimal residual disease in their autografts are in complete remission, while two of three patients reinfused with t(14;18) positive cells after purging, experienced a fast and aggressive relapse. As found by others, our data suggest that reinfusion of tumour-free autografts obtained by efficient in vivo purging using chemotherapy before harvesting, and/or by in vitropurging of the stem cell products, influence the patients remission status after HDT. (+info)