Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus.

The gene for the mitochondrial enzyme ornithine transcarbamylase was mapped to the short arm of the X chromosome by in situ hybridization experiments, with DNA complementary to the human ornithine transcarbamylase gene used as a probe. A series of cell lines with X chromosome abnormalities was used to localize the gene to band Xp21.1. Because the gene maps near the Duchenne muscular dystrophy locus, the ornithine transcarbamylase probe may be useful in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy as well as of ornithine transcarbamylase deficiency.

Deep venous thrombosis and pulmonary embolism after anterior cruciate ligament reconstruction: incidence, outcome, and risk factors.

AIMS: The aim of this study was to investigate the incidence, risk factors, and outcome of venous thromboembolism (VTE) following anterior cruciate ligament (ACL) reconstruction in a nationwide cohort. PATIENTS AND METHODS: All ACL reconstructions, primary and revision, that were recorded in the Swedish Knee Ligament Register (SKLR) between 2006 and 2013 were linked with data from the Swedish National Board of Health and Welfare. The incidence of VTE was determined by entries between the day of surgery until 90 days postoperatively based on diagnosis codes and the prescription of anticoagulants. Risk factors, outcome, and the use of thromboprophylaxis were analyzed. Descriptive statistics with multivariate analysis were used to describe the findings. RESULTS: The cohort consisted of 26 014 primary and revision ACL reconstructions. There were 89 deep venous thromboses (DVTs) and 12 pulmonary emboli (PEs) with a total of 95 VTEs (0.4 %). Six patients with a PE had a simultaneous DVT. The only independent risk factor for VTE was age greater than or equal to 40 years (odds ratio 2.31, 95% confidence interval 1.45 to 3.70; p < 0.001). Thromboprophylaxis was prescribed to 9461 patients (36%) and was equally distributed between those with and those without a VTE (37.9% vs 36.4%). All patient-reported outcome measures (PROMs) one and two years postoperatively were significantly lower in those with VTE. CONCLUSION: The incidence of VTE following ACL reconstruction is 0.4%, and the only significant risk factor is age. Patients with VTE had worse postoperative clinical outcome than patients without VTE. We recommend against the routine use of thromboprophylaxis, but it should be considered in older patients.

Human U1 small nuclear RNA pseudogenes do not map to the site of the U1 genes in 1p36 but are clustered in 1q12-q22.

Human U1 small nuclear RNA is encoded by approximately 30 gene copies. All of the U1 genes share several kilobases of essentially perfect flanking homology both upstream and downstream from the U1 coding region, but remarkably, for many U1 genes excellent flanking homology extends at least 24 kilobases upstream and 20 kilobases downstream. Class I U1 RNA pseudogenes are abundant in the human genome. These pseudogenes contain a complete but imperfect U1 coding region and possess extensive flanking homology to the true U1 genes. We mapped four class I pseudogenes by in situ hybridization to the long arm of chromosome 1, bands q12-q22, a region distinct from the site on the distal short arm of chromosome 1 to which the U1 genes have been previously mapped (Lund et al., Mol. Cell. Biol. 3:2211-2220, 1983; Naylor et al., Somat. Cell Mol. Genet. 10:307-313, 1984). We confirmed our in situ hybridization results by genomic blotting experiments with somatic cell hybrid lines with translocation products of human chromosome 1. These experiments provide further evidence that class I U1 pseudogenes and the true U1 genes are not interspersed. The results, along with those published elsewhere (Bernstein et al., Mol. Cell. Biol. 5:2159-2171, 1985), suggest that gene amplification may be responsible for the sequence homogeneity of the human U1 gene family.

Regulation of the capacity for O6-methylguanine removal from DNA in human lymphoblastoid cells studied by cell hybridization.

Hybrids were made between a ouabain-resistant, thioguanine-resistant human lymphoma line able to remove O6-methylguanine from its DNA (Mex+) and human lymphoblastoid lines deficient in this capability (Mex-). The formation of hybrids was confirmed by chromosomal analysis. Hybrid cells had an O6-methylguanine removal capacity per mole of guanine about one third to one half that of the Mex+ parents, i.e., about the same per cell. Cell hybrids removed the same amount of the alkylation adduct 3-methyladenine as did their parents per mole of guanine, i.e., about twice as much per cell. Although the cell hybrids had intermediate resistance to the cytotoxic action of N-methyl-N'-nitro-N-nitrosoguanidine used to induce O6-methylguanine and 3-methyladenine, there is evidence that the ability to remove O6-methylguanine and resistance to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine are dissociable characteristics.

Metanephric adenosarcoma in a young adult: morphologic, immunophenotypic, ultrastructural, and fluorescence in situ hybridization analyses: a case report and review of the literature.

Metanephric neoplasms are uncommon renal tumors that arise in both children and adults. They may be composed of small epithelial cells or benign stroma, or both, and are termed metanephric adenoma, metanephric stromal tumor, or metanephric adenofibroma, respectively. Thus far, these tumors have been known for their benign behavior. We present the case of a 21-year-old woman who developed a neoplasm composed of a renal epithelial component identical to metanephric adenoma combined with a malignant spindle cell sarcoma. The epithelial component was positive for pankeratin AE1/3, whereas the sarcomatous component was negative for epithelial markers and positive for vimentin, CD34, and CD117. No smooth muscle differentiation was apparent in the sarcoma by immunohistochemistry or ultrastructural analysis. By fluorescent in situ hybridization analysis of the sarcomatous component there was monosomy of the X chromosome, but no apparent variation from the normal diploid pattern for chromosomes 3, 7, 12, and 17. We conclude that the spectrum of metanephric neoplasia should be expanded to include malignant stromal variants, and we propose the term "metanephric adenosarcoma" for the present case.

Genomic imprinting in disorders of growth.

This review has briefly considered some of the vast amount of information that has been gathered on genomic imprinting and its role in PWS, AS, BWS and Russell-Silver syndrome. The pace of investigation into the phenomenon of imprinting will undoubtedly continue, because our understanding remains far from complete. Newer approaches to identifying imprinted genes based on their expression rather than their location are likely to uncover currently unknown genes. We can also look forward to more insight into the fascinating complexities of the imprinting process.

Diagnosis of Angelman syndrome in infants.

The diagnosis of Angelman syndrome (AS) has seldom been made in infants because the previously described characteristic manifestations usually are not apparent until after age 2 years. We describe 4 AS patients, one of whom has oculocutaneous albinism, who were less than 2 years old when first evaluated. All 4 have deletions of the region q11.2-q13 of chromosome 15. In the 3 cases in which parents were available for study the deleted chromosome 15 was maternally derived, as determined by cytological markers. All of the patients presented with severe to profound global developmental delay and postnatal-onset microcephaly; they had seizures, hypotonia, hyperreflexia, and hyperkinesis. All were hypopigmented as compared to their relatives. Each had eye abnormalities; all had choroidal pigment hypoplasia. None were initially described as having an abnormal appearance. We believe that AS is far more common than previously thought and present these 4 children to emphasize the manifestations that may be helpful in making the diagnosis in the young patient. We also emphasize the hypopigmentation that patients with AS frequently have, including what we think is the first reported case of albinism and AS.

Two patients with overlapping de novo duplications of the long arm of chromosome 9, including one case with Di George sequence.

Duplications of chromosome 9q are rare. We describe the cytogenetic and phenotypic findings in 2 patients, one with a large duplication covering most of 9q(q12-q33.2) and one with a smaller duplication (q21.12-q22.1) who had Di George sequence (DGS). The chromosome 9 origin of the extra material in the second case was confirmed by fluorescence in situ hybridization (FISH) analysis with a whole chromosome 9 paint. Microdeletions of chromosome 22 are common in DGS and have been reported in CHARGE association. This is the first report of an association of a chromosome 9 abnormality with DGS in the absence of a chromosome 22 abnormality and the seventh report of a patient with a duplication of a large portion of 9q (q11-q13 to q32-q33).

Novel isodicentric chromosome 18 in an abnormal infant with a mosaic karyotype [46,XY/46,XY,-18,+dic(18)(q12.2]).

A previously unreported isodicentric chromosome 18 was discovered in an abnormal infant boy whose mosaic karyotype was 46,XY/46,XY,-18,+idic(18)(q12.2). His constellation of congenital anomalies was typical of the 18q-syndrome. The clinical and cytogenetic characteristics of this patient are reported, and the literature concerning isochromosomes of 18 is reviewed.

Do NF1 gene deletions result in a characteristic phenotype?

Neurofibromatosis-1 (NF1) is an autosomal dominant disorder with marked variability of expression. Analysis of the NF1 gene (NF1) has detected a variety of mutations without any clear correlation with phenotype. However, deletions which remove all of NF1 have been reported in a small number of patients who have minor facial abnormalities, mental retardation, learning disabilities, and early or excessive burden of cutaneous or plexiform neurofibromas. The purpose of this study was to determine whether these phenotypic traits are associated with whole gene deletions. Out of 406 of our NF1 patients, 70 patients had manifestations previously associated with gene deletions. Thirty-five of these patients from 26 families were available for study. By fluorescence in situ hybridization (FISH) analysis, 4 were found to have deletions of the entire gene, including 2 sporadic cases, 1 familial case, and 1 case where family history could not be verified. In addition, the mother of the familial case was found to be mosaic for the deletion. Our results suggest that although large NF1 deletions occur with relatively high frequency in patients with certain findings, the presence of a deletion cannot be predicted solely on the basis of clinical phenotype.

Monosomy 22 in two ovarian granulosa cell tumors.

Cytogenetic studies of ovarian sex cord stromal cell tumors, although limited in number, have found trisomy 12 to be a recurring abnormality, especially in fibromas and granulosa cell tumors (GCTs). However, recent fluorescence in situ hybridization (FISH) studies have failed to confirm a high prevalence of trisomy 12 in GCTs. We describe the karyotypic findings in one adult and one juvenile GCT. Only the juvenile GCT had an extra, abnormal chromosome 12, but both the adult and juvenile GCT had monosomy 22. In light of these findings and the data in the literature, we suggest that monosomy 22 may be important in the genesis of these relatively rare tumors.

Chromosome replication in normal and transformed human lymphocytes.

We analyzed the late-replication patterns of human B-lymphocyte chromosomes before and after transformation by Epstein-Barr virus. There were no statistically significant differences between normal cells and transformed cells derived from the same male individual; therefore, the order of termination of chromosome replication was unchanged by transformation. We also examined the replication patterns of T lymphocytes from the same donor and found no differences between normal B and T cells.

der(3)t(3;5). Another recurring abnormality in myelodysplastic disorder.

Monosomy for chromosome 5 or a portion of the long arm is a common finding in acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndrome (MDS), especially when the disorder is therapy related [1,2]. If only a portion of chromosome 5 is missing, the loss is usually accomplished by interstitial deletion of various bands, most frequently q12-14 to q31-33 [3]. Occasionally monosomy for 5q is the result of a translocation between chromosome 5 and another chromosome, with the loss of the derivative chromosome that contains 5q. A previously described unbalanced translocation involves chromosome 7: [der(5)t(5;7)(q11.2;p11.2)] and appears to be a recurring abnormality in these disorders [4]. We report here one case of therapy related MDS, one case of MDS which may be therapy related, and two cases of MDS with another "variant" 5q - abnormality, namely a derivative chromosome 3 composed of most of the short arm of chromosome 5 and the long arm of chromosome 3: [der(3)t(3;5)(?p11;?p11)].

Chimerism as the etiology of a 46,XX/46,XY fertile true hermaphrodite.

OBJECTIVE: To determine the conceptional events resulting in a 46,XX/46,XY true hermaphrodite and to report the first pregnancy in a 46,XX/46,XY true hermaphrodite with an ovotestis. DESIGN: Chromosome studies were performed on patient lymphocytes and fibroblasts. Red cell antigens, human leukocyte antigens, and presence of Y-chromosome deoxyribonucleic acid were analyzed. Findings were compared with parental and sibling blood group data. SETTING: Genetics clinic and laboratories of a university hospital. RESULTS: These studies demonstrated that our patient is a chimera, with dual maternal and paternal contributions. In addition, despite the presence of an ovotestis, she conceived and delivered a child. CONCLUSIONS: The mechanism for chimerism in this case could be fertilization of (1) the secondary oocyte and first polar body; (2) the ovum and first polar body; (3) the ovum and second polar body; or (4) fusion of two embryos.

Nosocomial spread of hepatitis B virus (HBV) in a haemodialysis unit confirmed by HBV DNA sequencing.

An outbreak of hepatitis B virus (HBV) infection in a haemodialysis unit is described. Four patients in the unit contracted subclinical HBV infection within three months. DNA sequence analysis of the S gene of HBV isolates from chronic carriers and newly infected patients in the unit aided in tracing possible transmission pathways. Three newly infected patients had received partial or complete HBV vaccination previously. HBV was rapidly cleared from all three although the anti-HBs titre had not reached 10 IU L-1 in any of them at the time of infection.

Borrelia antibodies in children evaluated for Lyme neuroborreliosis.

BACKGROUND: We wanted to elucidate the value of Borrelia antibodies in serum and cerebrospinal fluid (CSF) for the diagnosis of Lyme neuroborreliosis (LNB). MATERIAL AND METHODS: We analyzed the serological findings, by anti-flagellin assay, in 267 patients with neurological symptoms from the Stockholm area, where Lyme borreliosis is endemic. RESULTS: In the 70 children with LNB, intrathecal Borrelia antibody production was diagnostic and found in 50 (71%). Sixteen (23%) showed an elevated antibody titer in serum only, and 4 (7%) had no serologic findings. Borrelia IgG in serum, with or without concomitant IgM, was a specific (98%), but insensitive (43%) marker of infection. Isolated, false-positive serum IgM titers were common and found in 10 of 67 children (15%) with viral meningitis, as well as in 28 of 111 (25%) with various neurological symptoms and normal CSF. The specificity of an isolated Borrelia IgM titer in serum was 81%, and the positive predictive value for Borrelia infection only 50% in our material. On the other hand, absence of antibodies in blood had a negative predictive value of 94%, which increased to 97% if also CSF findings were included. CONCLUSIONS: Intrathecal antibody production is strongly supportive of an LNB diagnosis. Conversely, isolated, elevated levels of Borrelia IgM in serum occur in up to one-fourth of children with various neurological complaints, and should be interpreted with caution, especially in nonendemic areas.