Clonal cytogenetic progression within intratumorally heterogeneous meningiomas predicts tumor recurrence.

Meningiomas arise from the coverings of the brain or the spinal cord. They are mostly benign and can be surgically cured. However, in approximately 5% of the cases, they turn into malignant forms with aggressive clinical behavior and increased risk of tumor recurrence. Cytogenetically meningiomas are well characterized, with normal karyotype or monosomy of chromosome 22 in most tumors and clinically relevant secondary losses of other autosomes and sex chromosomes in a subset of anaplastic tumors. Statistical analyses were performed for 1064 karyotypes derived from 661 meningiomas with respect to progression, and recurrence of the tumor. The order of accumulating genetic aberrations has previously been biostatistically estimated with oncogenetic tree models, and a genetic progression score derived from these models was shown to be predictive for tumor recurrence. Although more homogeneous than other cancer types, meningiomas show considerable intratumoral cytogenetic heterogeneity, particularly in their anaplastic form. We observed different cytogenetic patterns in tumor cells of 224 out of 661 (33.4%) meningiomas. The present study demonstrates that it is not sufficient to consider only the most frequent cytogenetic pattern observed in a sufficient set of cells derived from the same tumor. Even a single cell with more advanced genetic progression may start a clone and indicates also clinical progression. Cox regression analysis reveals that the clone with most advanced progression is a leading marker for recurrence in meningiomas. The aim of this study was the analysis of genetic heterogeneity on single cell basis. Further we investigated if there is a substantial correlation between the intratumoral heterogeneity of a given meningioma and its recurrence risk. We were able to show that the selection of single genetically advanced cells improves the prediction of clinical meningioma progression in a more precise manner.

Polymorphisms in the IGF1 signalling pathway including the myostatin gene are associated with left ventricular mass in male athletes.

BACKGROUND: Athlete's heart as an adaptation to long-time and intensive endurance training can vary considerably between individuals. Genetic polymorphisms in the cardiological relevant insulin-like growth factor 1 (IGF1) signalling pathway seem to have an essential influence on the extent of physiological hypertrophy. OBJECTIVE: Analysis of polymorphisms in the genes of IGF1, IGF1 receptor (IGF1R) and the negative regulator of the cardiac IGF1 signalling pathway, myostatin (MSTN), and their relation to left ventricular mass (LVM) of endurance athletes. METHODS: In 110 elite endurance athletes or athletes with a high amount of endurance training (75 males and 35 females) and 27 male controls, which were examined by echocardiographic imaging methods and ergometric exercise-testing, the genotypes of a cytosine-adenine repeat polymorphism in the promoter region of the IGF1 gene and a G/A substitution at position 3174 in the IGF1R gene were determined. Additionally, a mutation screen of the MSTN gene was performed. RESULTS: The polymorphisms in the IGF1 and the IGF1R gene showed a significant relation to the LVM for male (IGF1: p=0.003; IGF1R: p=0.01), but not for female athletes. The same applies to a previously unnoticed polymorphism in the 1 intron of the MSTN gene, whose deletion allele (AAA→AA) appears to increase the myostatic effect (p=0.015). Moreover, combinations of the polymorphisms showed significant synergistic effects on the LVM of the male athletes. CONCLUSIONS: The authors' results argue for the importance of polymorphisms in the IGF1 signalling pathway in combination with MSTN on the variant degree of physiological hypertrophy of male athletes.

Correspondence of tumor localization with tumor recurrence and cytogenetic progression in meningiomas.

OBJECTIVE: Meningiomas are mostly benign tumors that originate from the coverings of the brain and spinal cord. Cytogenetically, they reveal a normal karyotype or, typically, monosomy of chromosome 22. Progression of meningiomas is associated with a non-random pattern of secondary losses of other autosomes. Deletion of the short arm of one chromosome 1 is a decisive step to anaplastic growth in meningiomas. METHODS: Statistical analyses were performed for the karyotypes of 661 meningiomas with respect to localization, progression, and recurrence of the tumor. A mathematical mixture model estimates typical pathogenetic routes in terms of the accumulation of somatic chromosome changes in tumor cells. The model generates a genetic progression score (GPS) that estimates the prognosis as related to the cytogenetic properties of a given tumor. RESULTS: In 53 patients, one or several recurrences were documented over the period of observation. This corresponds to a total rate of recurrence of 8.0% after macroscopically complete tumor extirpation. Higher GPS values were shown to be strongly correlated with tumor recurrence (P = 2.9 x 10(-7)). High-risk tumors, both in terms of histology and cytogenetics, are localized much more frequently at the brain surface than at the cranial base (P = 1.2 x 10(-5) for World Health Organization grade and P = 3.3 x 10(-12) for GPS categorization). CONCLUSION: The tendency of cranial base meningiomas to recur seems to depend on surgical rather than biological reasons. As a quantitative measure, the GPS allows for a more precise assessment of the prognosis of meningiomas than the established categorical cytogenetic markers.

Application of oncogenetic trees mixtures as a biostatistical model of the clonal cytogenetic evolution of meningiomas.

Meningiomas are mostly benign tumors that originate from the coverings of brain and spinal cord. Typically, they reveal a normal karyotype or monosomy for chromosome 22. Rare clinical progression of meningiomas is associated with a nonrandom pattern of secondary losses of other autosomes. Deletion of the short arm of one chromosome 1 appears to be a decisive step for anaplastic growth in meningiomas. We calculated an oncogenetic tree model that estimates the most likely cytogenetic pathways of 661 meningioma patients in terms of accumulation of somatic chromosome changes in tumor cells. The genetic progression score (GPS) estimates the genetic status of a tumor as progression in the corresponding tumor cells along this model. Large GPS values are highly correlated with early recurrence of meningiomas [p < 10(-4)]. This correlation holds even if patients are stratified by WHO grade. We show that tumor location also has an impact on genetic progression. Clinical relevance of the GPS is thus demonstrated with respect to origin, WHO grade and recurrence of the tumor. As a quantitative measure the GPS allows a more precise assessment of the prognosis of meningiomas than categorical cytogenetic markers based on single chromosomal aberrations.

Attitudes of mothers towards their child with Down syndrome before and after the introduction of prenatal diagnosis.

In 1970, before the introduction of prenatal diagnosis of chromosome anomalies, an unpublished questionnaire study concerning the social and emotional situation of mothers of children with Down syndrome was conducted in southern Germany. To assess the psychosocial impact of the availability of prenatal diagnosis on parents of genetically handicapped children, we re-evaluated and repeated the 1970 study over 30 years later. Although mothers' feelings of guilt for having a child with disabilities remained on a low level, today's mothers have a stronger feeling of being involuntarily segregated in society. On the other hand, they more often experience support and respect from outside, particularly through self-support groups; moreover, tendencies of active withdrawal from social life have decreased.

Hyperdiploidy defines a distinct cytogenetic entity of meningiomas.

BACKGROUND: The most common chromosomal aberration found in meningiomas is monosomy 22. Progression and recurrence of meningiomas are usually associated with additional chromosome losses. Rarely, however, meningiomas have strongly hyperdiploid karyotypes with over 50 chromosomes; the objective of this study was to explore the cytogenetic and histopathologic patterns as well as the clinical significance of hyperdiploidy in meningiomas. METHODS: Within a series of 677 consecutive meningiomas, we identified a subgroup comprising 16 cases that display a strikingly uniform pattern of hyperdiploidy mostly without structural chromosome rearrangements, as shown by banding techniques and, in the single structurally aberrant case, spectral karyotyping. RESULTS: These meningiomas each have between 50 and 56 chromosomes, with trisomy 12 (14/16 cases), trisomy 20 (13/16 cases), trisomy 5 (12/16 cases), and trisomy 17 (10/16 cases). Histomorphologically, hyperdiploid meningiomas feature a heterogeneous phenotype. However, they are associated with a higher histological grade, and decreased expression of alkaline phosphatase as compared to meningiomas with typical karyotype. In two patients, recurrences were documented and three patients died of disease during the period of observation, indicating a worse prognosis of hyperdiploid than of cytogenetically typical meningiomas. CONCLUSION: We conclude that hyperdiploidy constitutes a small but clinically relevant entity of biologically aggressive meningiomas, which are cytogenetically distinguishable from the majority of common-type meningiomas.

Different mechanisms of mitotic instability in cancer cell lines.

Chromosomes of human malignant tumours display not only structural recombinations but also a wide variety of mostly non-random numerical aberrations. However, only little is known about the mechanisms leading to recurrent aneuploidies. We therefore investigated whether the malsegregation of specific chromosomes is due to a defect of the mitotic spindle apparatus. We analyzed mitoses of cell lines of six gliomas and of one breast carcinoma by combined immunohistochemistry and fluorescence in situ hybridization for non-disjunction of chromosomes 7, 8, 10, 12, 17, and 18 and observed three different phenomena. i) Five of six glioma cell lines showed a bipolar spindle but displayed a chromosome-specific malsegregation of all chromosomes studied with high but significantly different frequencies. Chromosomes 7 and 8 showed non-disjunction in about 75 and 50%, respectively. Although chromosomes 10, 12, 17, and 18 displayed equal separation during mitosis in 72, 86, 73, and 78%, respectively, a relevant percentage of an average of 24% of dividing cells showed even malsegregation of these chromosomes. ii) Only one of the glioma cell lines displayed multipolar spindles in one-third of the investigated cells resulting in non-specific aneuploidy. iii) The breast cancer cell line MCF7 displayed a bipolar spindle, but high frequencies of non-disjunction of all six investigated chromosomes but without preferential loss or gain of specific chromosomes indicating a different mechanism of chromosome malsegregation. In a small percentage of mitoses the chromatids of both homologous chromosomes were not separated mimicking the mechanism in the first meiotic division. This mechanism of double non-disjunction, not detectable by conventional cytogenetic analysis, procreates cell clones with genomic separation for particular chromosomes resulting in homozygosity for mutations which had been present heterozygously in the initial tumour cells.

Histopathologic indicators of recurrence in meningiomas: correlation with clinical and genetic parameters.

Meningiomas in general are circumscribed slow-growing tumors. However, despite gross total resection, tumor relapse and patients' outcome are still an issue. Risk stratification based on histomorphology alone remains problematic. This study explored the independent prognostic value of potential risk factors among 206 patients who underwent meningioma resection and followed-up until death or a median of 44 months. The statistical analysis considered clinical data, histomorphologic parameters, cytogenetic findings, Ki-67 immunoreactivity, and activity of tissue non-specific alkaline phosphatase (ALPL). Recurrence-free survival estimates were computed and prognostic factors were identified using Cox proportional hazards model. Independent predictors of recurrence included (1) anaplasia; (2) mitotic index > or =20/10 high-power fields; (3) subtotal tumor resection; (4) loss of short arm of chromosome 1 (1p-); and (5) Ki-67 labeling index (LI) >12%. Among totally resected WHO grade I meningiomas, neither histopathologic nor clinical parameters were predictive, whereas 1p- was the only independent prognostic factor. ALPL did not reach significance in the multivariate modeling, however, the fast and low-cost histochemical detection of ALPL expression could be proved as a highly sensitive screening method for 1p-. In particular, biologically aggressive meningiomas of histologically benign or "borderline" phenotype could be therefore identified by ALPL detection followed by 1p in situ hybridization.

Intratumoral genetic heterogeneity in pilocytic astrocytomas revealed by CGH-analysis of microdissected tumor cells and FISH on tumor tissue sections.

Pilocytic astrocytomas are the most frequent gliomas of childhood. The majority of cases show cytogenetic normal karyotypes. Although in diffuse gliomas TP53 gene mutations or deletions occur with significant frequency, the role in pilocytic astrocytomas remains unclear. Histomorphologically different areas of 14 pilocytic astrocytomas were microdissected and analyzed for genetic aberrations and heterogeneity. CGH analysis revealed gains of chromosome arm 4q and 6q mainly in areas of classic biphasic pattern, whereas pleomorphic areas presented gains of chromosome 6 and 8q. Using two-color fluorescence in situ hybridization (FISH) the spatial distribution of aneuploidies for chromosomes 7, 8, 17 and the TP53 gene were assessed on parallel sections. FISH analysis revealed a significant percentage of cells with interspersed heterozygous deletions of TP53 in all tumors (14/14), ten cases showed also monosomy 17. Besides gains of chromosomes 7 and 8, losses of these chromosomes were detected in the majority of tumors. In conclusion, pilocytic astrocytomas show a genetic heterogeneity associated with variations of histologic structure as well as an intratumoral heterogeneity observed on single cell level by FISH.

Human endogenous retrovirus HERV-K(HML-2) Rec expression and transcriptional activities in normal and rheumatoid arthritis synovia.

OBJECTIVE: Despite abundance in the genome, the possible functions of human endogenous retrovirus (HERV) sequences are not well understood. The involvement of HERV in various disease conditions, such as germ cell tumors or autoimmune diseases like rheumatoid arthritis (RA), has been suggested. We investigated expression of HERV-K(HML-2) env-derived transcripts in normal and RA synovia. METHODS: We analyzed HERV-K(HML-2) expression on the mRNA and protein level by RT-PCR analysis and immunofluorescence labeling of the HERV-K(HML-2) Rec (formerly cORF) protein. We examined synovial cell cultures from normal synovia (n = 9), from patients with RA (n = 26), and osteoarthritis (OA, n = 4), and uncultured synovial tissues (RA, n = 12; normal synovia, n = 1). RESULTS: HERV-K Rec protein was expressed in all normal synovial specimens, and in the majority of RA and OA cases. We demonstrate for the first time expression of HERV-K protein in synovial tissue. RT-PCR and sequence analysis of cloned RT-PCR products confirmed expression of spliced HERV-K(HML-2) env transcripts in normal and in arthritic synovia. In addition to rec mRNA, several alternatively spliced transcripts, including np9, were identified. However, different amounts of the various RT-PCR products indicate different expression levels of HERV-K(HML-2) env-derived transcripts in RA compared to normal synovia, with apparently lower expression levels in arthritic synovia. CONCLUSION: These findings imply a physiological role of HERV-K(HML-2) Rec in synovial tissue. Differences in the expression of HERV-K env-derived transcripts in RA synovia may be caused by disease-specific changes in the general expression pattern.

Patients with high-grade gliomas harboring deletions of chromosomes 9p and 10q benefit from temozolomide treatment.

Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ) chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group) and 30 patients received radiotherapy alone (RT group). The most common aberrations detected were gains of parts of chromosome 7 and losses of 10q, 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months). Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.

Detailed chromosomal characterization of the breast cancer cell line MCF7 with special focus on the expression of the serine-threonine kinase 15.

Although the cell line MCF7 is widely used in breast cancer research, its cytogenetic properties have not been thoroughly investigated so far. As conventional G-banding analysis cannot resolve the complex chromosome aberrations, we investigated MCF7 cells using molecular-cytogenetic methods, with particular attention to the DNA amplification site on chromosome 20q. With spectral karyotyping we found numerous unbalanced chromosome translocations, and with comparative genomic hybridization we detected many quantitative genomic imbalances. Furthermore, we analyzed the amplified region at 20q with the candidate tumour susceptibility gene STK15 in detail by fluorescence in situ hybridization, whole chromosome painting, immunohistochemistry, Western blot and expression analysis. In MCF7 interphase cells we found increased copy number of the STK15 gene associated with overexpression of STK15 mRNA. Accordingly, STK15 protein is overexpressed as compared to normal human fibroblasts in Western blot analysis. Overexpression of STK15 mRNA and protein is disproportionally stronger than that expected from the single additional copy of the STK15 gene. These data indicate that the highly increased level of STK15 protein in MCF7 cannot be explained by gene amplification alone. Apparently, secondary mechanisms of gene up-regulation are involved. This observation may be of general interest with regard to the activation of oncogenes in tumour cells.

Interstitial loss and gain of sequences on chromosome 22 in meningiomas with normal karyotype.

In nearly half of sporadic low grade meningiomas no chromosome aberration can be detected. In the majority of the other half chromosome 22 is lost. In higher grade meningiomas this loss is followed by characteristic secondary chromosome aberrations. Regarding the molecular findings in Schwannomas, homozygous loss or mutation of the NF2 gene located on chromosome 22, was supposed also to be the primary event in meningioma development. However, in nearly all high grade but in only a minority of low grade meningiomas the loss of the NF2 protein is observed. Therefore, both the hypothetical combined heterozygous loss of or inactivation of two or more tumour suppressor genes (at least one of them located on chromosome 22) or the homozygous loss of a regulatory gene on chromosome 22 different from NF2 was discussed. In search for microdeletions or/and structural recombinations of chromosome 22 we investigated primary cell cultures of 43 meningiomas by conventional G-banding (26 without, 17 with loss of chromosome 22). Twenty-seven tumours were analysed with spectral karyotyping (SKY) and 16 with fluorescence in situ hybridisation (FISH) with DNA probes for the chromosomal regions of 22q11.2, 22q11.23q12.1, 22q12.1 and 22q13.3. SKY analysis confirmed G-banding data for chromosome 22 and could specify marker chromosomes and translocations containing material from chromosome(s) 22. Confirming our assumption microdeletions on chromosome 22 were detected by FISH in 6/8 cytogenetically non-aberrant meningiomas. Surprisingly, in 2/8 cases we observed gains of the 22q13.3 and in 2/8 gains of the 22q12.1 region. Here we present first evidence for an uncommon mechanism during early meningioma development at least for a meningioma subgroup: i) duplication and translocation of sequences from chromosome 22 to different chromosomes. ii) deletion of the original sequences on chromosome 22, resulting in disomy again (only visible as translocation in metaphase FISH). iii) loss of chromosome 22.

Overexpression and amplification of STK15 in human gliomas.

The serine/threonine kinase 15 (STK15) at chromosome 20q13.2 is frequently shown to be amplified and overexpressed in several human cancers. STK15 has been reported to act as a cell cycle regulator and its overexpression induces centrosome amplification and aneuploidy. Recently we showed that STK15 even plays a role in human malignant brain tumours and we described an amplification of the gene in 31% of the investigated gliomas. In this study we scrutinized the correlation of increased STK15 on DNA and mRNA levels in gliomas of different histological grades. Southern blotting confirmed the amplification frequency of the STK15 gene, which had been previously detected by comparative PCR. In total, DNA gains were found in 26% of the investigated gliomas. Interestingly, we detected overexpression of STK15 mRNA in 60% of the analyzed brain tumours. The elevated expression does not strongly correlate with gains on DNA level, but all cases with an amplification of the STK15 gene display overexpression. Gains of the STK15 gene seem to occur irrespectively of the histological grades of the tumours, so that STK15 probably is not a progression associated factor. Amplification and overexpression of the kinase rather represent a primary alteration in human gliomas, which could play an important role as an early event in all glioma subtypes.

Somatic mosaicism of chromosome 7 in a highly proliferating melanocytic congenital naevus in a ring chromosome 7 patient.

Ring chromosome 7 is a rare but well documented chromosomal aberration in man. So far at least 14 cases have been reported in the literature showing a variable but distinct pattern of phenotypic characteristics in affected individuals. Besides others, skin findings as pigmented naevi are especially frequent. Loss of chromosomal material from the terminal chromosome arms in the structurally abnormal ring chromosome 7 as well as somatic mosaicism with loss or gain of chromosome 7 has been suggested to be responsible for the clinical symptoms. We now report another case of a ring chromosome 7 in a 14-year-old boy with multiple remarkable congenital naevi, where we could demonstrate for the first time somatic mosaicism showing significant gain of chromosome 7 within a highly proliferating melanocytic congenital naevus (MCN).

Replicative multivirus infection with cytomegalovirus, herpes simplex virus 1, and parvovirus B19, and latent Epstein-Barr virus infection in the synovial tissue of a psoriatic arthritis patient.

BACKGROUND: Psoriatic arthropathy occurs as complicating feature in about 5-7% of psoriasis patients. Infectious mechanisms including viral antigens have been suggested by serologic data as CD8 T cellular specifity towards viral epitopes. OBJECTIVE AND RESULTS: We here reported a case of a 32-year-old male psoriatic arthritis patient, where we could demonstrate simultaneous infection with cytomegalovirus (CMV), herpes simplex virus type I (HSV1) and parvovirus B19 (B19), as well as latent Epstein-Barr virus (EBV) infection within the synovial tissue by immunohistochemistry (CMV, parvovirus B19, HSV1, EBV-LMP) and DNA-in situ-hybridization (CMV). Serologic examination revealed positive EBV and parvovirus B19-IgG-antibodies, but no antibody response to HSV1 and CMV. CONCLUSION: This case is of special interest, since replicative viral infections have not yet been demonstrated localised in the psoriatic arthritis synovia. Thus, with particular regard to the limited information of the serologic data and the possible need of immuno suppressive therapy direct synovial testing for viral antigenes may be considered in psoriatic arthritis patients.

Human endogenous retrovirus HERV-K(HML-2) proviruses with Rec protein coding capacity and transcriptional activity.

The human endogenous retrovirus family HERV-K(HML-2) encodes the so-called Rec protein that displays functional similarities to the HIV(REV) protein. The number of proviruses producing Rec protein was hitherto unknown. We therefore analyzed the human genome sequence data and determined seven HERV-K(HML-2) proviruses potentially capable of producing Rec both on the mRNA and the protein level. We analyzed Rec mRNA expression in the Tera-1 cell line and in synovial tissue, and in the expressed sequence tag (EST) database. Diagnostic nucleotides assigned transcriptionally active and Rec-encoding proviruses to human chromosomes 6, 7, 11, and 12. Differently spliced mRNAs were also identified. The various active proviruses encode almost identical Rec proteins. Our study contributes to the understanding of the biology of HERV-K(HML-2) Rec protein. Our study further demonstrates that minor sequence differences among proviruses allow assigning HERV transcripts to particular proviral loci. Extended studies will eventually yield a more complete image of HERV transcription, regulation, and biological significance in diverse human tissues.

Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization.

In rheumatoid arthritis (RA) viral triggers, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV), have been suggested. By PCR analysis DNA of several viruses among which EBV, CMV, and parvovirus B19 (B19) has been detected in RA synovial fluid and synovial tissue. In 63 synovial tissues of 29 rheumatoid arthritis (RA), 6 psoriatic arthritis (PsA), 26 reactive arthritis/synovitis (rA/S), and two normal synovial cases, we recently could demonstrate a high percentage of replicative B19 infection within the synovial tissue, being significantly more frequent in autoimmune arthritis. To further investigate the influence of synovial virus infections in rheumatoid arthritis, we now analyzed the same sample of synovial tissues for CMV and EBV infections by DNA-in situ hybridization (CMV), EBER1/2-RNA-in situ hybridization (EBV), and immunohistochemistry. A significant latent EBV infection of synovial lining cells, synovial fibroblasts, and/or infiltrating lymphocytes was identified in 5/29 (17.2 %) RA, 1/6 (16.7%) PsA, and to a much lower degree in 1/26 (3.8%) rA/S specimens. CMV-DNA was detected in 31% of RA, 3/6 (50%) of PsA, and 11.5% of rA/S. Immunohistochemical analysis of CMV early antigen revealed replicative CMV activity in 20.7% of RA and 2/6 (33.3%) of PsA specimens but not in reactive arthritis synovia. Comparative analysis of the EBV-, CMV-, and published B19-data demonstrated that relevant synovial virus infections in general and furthermore double or multiple infections are far more common in autoimmune arthritis than in rA/S. A triple virus infection was found solely in RA in 10.3% of cases. The evidence of increased synovial persistence of EBV, CMV, or B19 either alone or even more as coinciding infections may further reinforce the notion of a primary role of these viruses in autoimmune arthritis.

Chromosomal translocation t(18;21)(q23;q22.1) indicates novel susceptibility loci for frontotemporal dementia with ALS.

A chromosomal translocation t(18;21)(q23;q22) is reported in a patient with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We exclude the physical involvement and silencing of the ALS-linked gene for copper/zinc superoxide dismutase (SOD1) on chromosome 21q22.1. The breakpoints are assigned to sequences flanked by the markers ATA1H06, D18S462, D21S1915, and D21S1898. These critical regions may contain susceptibility loci for FTD associated with ALS.

Parvovirus B19-related chronic monoarthritis: immunohistochemical detection of virus-positive lymphocytes within the synovial tissue compartment: two reported cases.

Apart from systemic symptoms of viral infection parvovirus B19, the infectious agent in erythema infectiosum, can lead to mainly self-limited acute and chronic arthropathy. Because mild subclinical features of the disease can be easily overlooked, joint affections might appear as isolated symptoms. We here report two cases of chronic monoarthritic symptoms of unknown origin, where immunohistochemical detection of B19-positive lymphocytic cells in the synovial tissue led to the diagnosis of B19 arthropathy. In conclusion, respective virus diagnostics should be considered even in chronic monosymptomatic arthritic lesions. The pathology of B19 arthropathy seems to be due to direct virus infection of cells within the synovia.