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S Sheldon

Publications and source records attributed to S Sheldon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal dysplasia in humans that has been mapped to the short arm of chromosome 6. We report linkage of a CCD mutation to 6p21 in a large family and exclude the bone morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic localization and genetic recombination. CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the BMP6 gene hybridized to chromosome 6 in band region p23-p24 using FISH analysis, placing this gene cytogenetically more distal than the region of linkage for CCD. We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family. The results confirm the map position of CCD on 6p21, further refine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene.

Bone Morphogenetic Protein 6↗
PubMed1997

Autosomal dominant microcephaly with normal intelligence, short palpebral fissures, and digital anomalies.

We describe a family segregating an autosomal dominant mutation producing a syndrome comprising microcephaly with normal intelligence and short palpebral fissures together with variable signs including thumb hypoplasia, shortness of the middle phalanges of the second and fifth fingers, small feet, a gap between the first and second toes, and mild syndactyly of the toes or fingers. A characteristic radiologic finding in our family is thinning of the proximal end of the first metacarpal and shortening of that metacarpal. The severity of these findings was asymmetric in our patients. This syndrome is similar to patients described by Brunner and Winter [1991: J Med Genet 28: 389-394], Feingold [1975: Synd Ident 3:16-17, 1978: Hosp Prac 13:44-49], and König et al. [1990: Dysmorphol Clin Genet 4:83-86].

Child, Preschool↗
PubMed1996

Cytogenetic and molecular analysis of inv dup(15) chromosomes observed in two patients with autistic disorder and mental retardation.

A variety of distinct phenotypes has been associated with supernumerary inv dup(15) chromosomes. Although different cytogenetic rearrangements have been associated with distinguishable clinical syndromes, precise genotype-phenotype correlations have not been determined. However, the availability of chromosome 15 DNA markers provides a means to characterize inv dup(15) chromosomes in detail to facilitate the determination of specific genotype-phenotype associations. We describe 2 patients with an autistic disorder, mental retardation, developmental delay, seizures, and supernumerary inv dup(15) chromosomes. Conventional and molecular cytogenetic studies confirmed the chromosomal origin of the supernumerary chromosomes and showed that the duplicated region extended to at least band 15q13. An analysis of chromosome 15 microsatellite CA polymorphisms suggested a maternal origin of the inv dup(15) chromosomes and biparental inheritance of the two intact chromosome 15 homologs. The results of this study add to the existing literature which suggests that the clinical phenotype of patients with a supernumerary inv dup(15) chromosome is determined not only by the extent of the duplicated region, but by the dosage of genes located within band 15q13 and the origin of the normal chromosomes 15.

Adolescent↗
PubMed1996

Ki-1 anaplastic large cell lymphoma with a prominent leukemic phase.

Patients with Ki-1 (CD30)-positive anaplastic large cell lymphoma (ALCL) occasionally have rare circulating lymphoma cells. We report a case of ALCL with a prominent leukemic phase. A 36-year-old man presented with widespread ALCL involving lymph nodes, spleen, pleural fluid, cerebrospinal fluid, and bone marrow. His white blood cell count was 106,000/mm3 with 20% lymphoma cells. The circulating neoplastic cells were large, and had irregular nuclei with multiple small nucleoli, ample cytoplasm, and multiple clear cytoplasmic vacuoles. This case illustrates that ALCL may have a marked leukemic phase composed of large anaplastic cells.

Adult↗
PubMed1996

Familial large vestibular aqueduct syndrome.

The large vestibular aqueduct syndrome (LVAS) is a distinct clinical entity characterized by stepwise progressive sensorineural hearing loss associated with isolated enlargement of the vestibular aqueduct. A correlative clinical, audiologic, vestibular, cytogenetic, and radiographic analysis of a family with inherited LVAS was performed. The male proband and his affected brother are offspring of unaffected parents, and have no other abnormalities. Pedigree analysis suggests autosomal recessive or X-linked inheritance with variable expressivity of LVAS in this family. This study is the first description of familial inheritance of LVAS. LVAS may account for a significant number of patients with nonsyndromal, genetic sensorineural hearing loss. Future molecular analyses of this study family may identify the causative gene(s) in LVAS.

Adult↗
PubMed1996

A new translocation, t(3;6)(q12;24) associated with chronic myelomonocytic leukaemia and marrow fibrosis.

This report describes a 75-year-old man with chronic myelomonocytic leukaemia (CMML) and marked marrow fibrosis associated with t(3;6)(q12;24). Although structural abnormalities of 3q occur in haematological neoplasia, this particular chromosomal translocation has not been previously described in CMML. Karyotypic abnormalities involving 3q and marrow fibrosis may affect prognosis in CMML.

Aged↗
PubMed1994

Rejection in heart transplantation strongly correlates with HLA-DR antigen mismatch.

It is well established that incompatible HLA antigens presented by donor tissue readily evoke an immune response. Prospective HLA matching policies, widespread in European kidney transplant centers have reduced the level of HLA mismatching and have significantly improved graft survival. The influence of HLA incompatibility in heart transplantation remains controversial, and prospective HLA matching is seldom achieved. We examined the role of HLA antigen mismatching on transplant rejection by analyzing 2569 endomyocardial biopsies (EMB) from 157 consecutive orthotopic heart transplants performed from April 1987 to August 1993 in our own center. Biopsies were graded according to the accepted International Classification, with grade 2 and higher indicating rejection. Among 91 patients who received a 2 HLA-DR mismatch transplant 34% of 1624 biopsies analyzed were graded as > or = 2. This frequency fell to 29% of 797 biopsies for 53 patients with a one-HLA-DR mismatch and to 18% of 148 biopsies for 13 patients in the zero-HLA-DR-mismatch group (P < 0.00005). No significant effect on EMB grade frequencies was observed using the same method of analysis with transplants mismatched at the HLA-A or HLA-B loci apart from analysis of HLA-B matched transplants at 3 months posttransplant (P = 0.02). The close linkage of the HLA-B and HLA-DR loci may account for this observation. The results of this study show that heart transplants matched at the HLA-DR locus have a significantly reduced incidence of EMB grades indicative of rejection requiring augmented immunosuppressive therapy. We propose that prospective HLA-DR matching should be adopted for allocation of donor hearts for more efficient use of this precious and limited resource.

Adolescent↗
PubMed1994

Unbalanced 5;16 translocation in a boy with papillary thyroid carcinoma.

This is the first reported case of an unbalanced chromosome rearrangement resulting in trisomy 5q35.5-->qter and monosomy 16p 13.3-->pter, in a boy with mental and growth retardation, minor anomalies, and a history of bilateral papillary thyroid carcinoma. This was the result of a familial balanced translocation. The clinical and cytogenetic manifestations of the case are presented and the possible role of the chromosomal rearrangement in the etiology of the thyroid carcinoma is discussed.

Abnormalities, Multiple↗
PubMed1994

Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen.

A 31-year-old renal transplant recipient developed an unusual T-cell lymphoproliferative disorder 3 years after transplantation. The neoplasm involved the spleen, without concomitant hepatomegaly, lymphadenopathy, or obvious bone marrow involvement. Peripheral blood involvement developed after splenectomy. Immunophenotypically, the neoplastic cells expressed CD2, CD3, CD7, CD16, CD45, CD56, and the gamma/delta T-cell receptor on the surface membrane. The neoplastic cells were negative for surface membrane CD4, CD5, and CD8. Serologic and/or DNA analyses for viruses, including Epstein-Barr virus, human T-cell lymphotropic virus-1, human immunodeficiency virus, and human herpesvirus-6, were negative. Cytogenetic findings included a translocation breakpoint at chromosome 7p15, consistent with involvement of the T-cell receptor gamma-chain locus. Although gamma/delta T-cell lymphomas have been reported to have a predilection for hepatosplenic localization, this is the first well-documented case to be described in the setting of posttransplantation immunosuppression.

Adult↗
PubMed1994

Therapy-related acute myeloid leukaemia following immunosuppression with azathioprine for polymyositis.

A 52-year-old man developed therapy-related acute myeloid leukemia (AML) following prolonged immunosuppression with azathioprine for polymyositis. Karyotypic analysis showed deletions of the short arm of chromosome 7 and the long arm of chromosome 5. The importance of recognizing this potential complication while treating benign rheumatological and immunological diseases with purine analogues like azathioprine is emphasized. Therapy-related AML is a poor prognostic group that does not respond favourably to standard induction therapy.

Acute Disease↗
PubMed1994

Do specific HLA antigens predispose to ischaemic heart disease or idiopathic dilated cardiomyopathy?

BACKGROUND: The aetiology of idiopathic dilated cardiomyopathy is believed to have an immunological component. Association with human leucocyte antigens (HLAs) has been previously reported, particularly with HLA-DR4. AIM: To determine the association of HLA type with diagnosis in a group of patients assessed for heart transplantation. METHODS: A comparison was made of frequencies of HLA types in patients with a diagnosis of idiopathic dilated cardiomyopathy or (n = 98) ischaemic heart disease (n = 170) and in controls from the North Western region (n = 857). RESULTS: Neither the patients with idiopathic dilated cardiomyopathy nor those with ischaemic heart disease showed a significant increase or decrease in any HLA frequency compared with the controls. CONCLUSION: These results suggest that there is no HLA association with idiopathic dilated cardiomyopathy or ischaemic heart disease. This conflicts with the results of some previous studies.

Cardiomyopathy, Dilated↗
PubMed1993

Mapping of the gene for interferon-inducible dsRNA-dependent protein kinase to chromosome region 2p21-22: a site of rearrangements in myeloproliferative disorders.

Recent evidence suggests that the human interferon-inducible double-stranded RNA-dependent protein kinase may function as a tumor suppressor. Here we describe the mapping of the gene for this kinase to chromosome region 2p21-22 by fluorescence in situ hybridization. A combined analysis of cytogenetic data from a series of 341 patients with hematologic disorders that exhibited cytogenetic abnormalities and from published reports indicates that abnormalities involving 2p21-22 occur nonrandomly and are observed among patients with acute myelogenous leukemia, raising the possibility of a role for this protein kinase in leukemogenesis.

Bone Marrow↗
PubMed1993

Discordant phenotype of two overlapping deletions involving the PAX3 gene in chromosome 2q35.

Waardenburg syndrome (WS), the most common form of inherited congenital deafness, is a pleiotropic, autosomal dominant condition with variable penetrance and expressivity. WS is clinically and genetically heterogeneous. The basis for the phenotypic variability observed among and between WS families is unknown. However, mutations within the paired-box gene, PAX3, have been associated with a subset of WS patients. In this report we use cytogenetic and molecular genetic techniques to study a patient with WS type 3, a form of WS consisting of typical WS type 1 features plus mental retardation, microcephaly, and severe skeletal anomalies. Our results show that the WS3 patient has a de novo paternally derived deletion, del (2)(q35q36), that spans the genetic loci PAX3 and COL4A3. A molecular analysis of a chromosome 2 deletional mapping panel maps the PAX3 locus to 2q35 and suggests the locus order: centromere-(INHA, DES)-PAX3-COL4A3-(ALPI, CHRND)-telomere. Our analyses also show that a patient with a cleft palate and lip pits, but lacking diagnostic WS features, has a deletion, del (2)(q33q35), involving the PAX3 locus. This result suggests that not all PAX3 mutations are associated with a WS phenotype and that additional regional loci may modify or regulate the PAX3 locus and/or the development of a WS phenotype.

Bone and Bones↗
PubMed1993

Acute biphenotypic leukaemia: immunophenotypic and cytogenetic analysis.

The incidence of acute biphenotypic leukaemia has ranged from less than 1% to almost 50% in various reports in the literature. This wide variability may be attributed to a number of reasons including lack of consistent diagnostic criteria, use of various panels of antibodies, and the failure to recognize the lack of lineage specificity of some of the antibodies used. The morphology, cytochemistry, immunophenotype and cytogenetics of acute biphenotypic leukaemias from our institution were studied. The diagnostic criteria took into consideration the morphology of the analysed cells, light scatter characteristics, and evaluation of antibody fluorescence histograms in determining whether the aberrant marker expression was arising from leukaemic blasts or differentiated bone marrow elements. Fifty-two of 746 cases (7%) fulfilled our criteria for acute biphenotypic leukaemias. These included 30 cases of acute lymphoblastic leukaemia (ALL) expressing myeloid antigens, 21 cases of acute myelogenous leukaemia (AML) expressing lymphoid markers, and one case of ALL expressing both B- and T-cell associated antigens. The acute biphenotypic leukaemia cases consisted of four major immunophenotypic subgroups: CD2+ AML (11), CD19+ AML (8), CD13 and/or CD33+ ALL (24), CD11b+ ALL (5) and others (4). Chromosomal analysis was carried out in 42/52 of the acute biphenotypic leukaemia cases; a clonal abnormality was found in 31 of these 42 cases. This study highlights the problems encountered in the diagnosis of acute biphenotypic leukaemia, some of which may be responsible for the wide variation in the reported incidence of this leukaemia. We suggest that the use of strict, uniform diagnostic criteria may help in establishing a more consistent approach towards diagnosis of this leukaemic entity. We also suggest that biphenotypic leukaemia is comprised of biologically different groups of leukaemia based on immunophenotypic and cytogenetic findings.

Adolescent↗
PubMed1990

Detection of Philadelphia chromosome-positive cells from glass slide smears using the polymerase chain reaction.

Southern and Northern blot hybridization studies and the polymerase chain reaction (PCR) have been used to analyze the bcr-abl gene complex in chronic myelogenous leukemia (CML). Because fresh or cryopreserved cells may not always be available for molecular analyses, we investigated the possibility of using routinely prepared glass slide smears of blood or bone marrow as our source of cellular material. Cellular RNA was prepared directly from the blood or bone marrow smears using a modified RNA extraction procedure. cDNA was synthesized from RNA and amplified with PCR using bcr and abl-specific primers. Using this procedure, the bcr-abl fusion gene was detected by PCR in 21 of 21 patients with CML. Three patients who had undergone allogenic bone marrow transplantation (BMT) for CML were also studied by PCR. bcr-abl was identified transiently in one patient, persisted in one patient after BMT for 2 years until relapse occurred, and was absent in one patient to 18 months after BMT. We have shown that PCR can detect the bcr-abl gene of CML using material from glass-slide smears. This technique may be useful as a general approach in evaluating archival hematologic specimens for the expression of critical gene products.

Bone Marrow Transplantation↗
PubMed1989

Are HLA antigens implicated in the pathogenesis of non-haemorrhagic deterioration following aneurysmal subarachnoid haemorrhage.

Aneursymal subarachnoid haemorrhage is frequently complicated by non-haemorrhagic deterioration. HLA typing was studied in a group of 40 patients who had sustained an aneurysmal subarachnoid haemorrhage in order to assess its ability to identify those who are likely to experience non-haemorrhagic deterioration. The antigen HLA-B7 appeared to be associated with an increased likelihood of this event supervening. Conversely, the antigen HLA-DR3, seemed to exert a "protective" influence.

Adult↗