Refine
Has Fulltext
- yes (58)
Is part of the Bibliography
- yes (58)
Year of publication
Document Type
- Journal article (56)
- Doctoral Thesis (1)
- Report (1)
Keywords
- CML (2)
- Neisseria gonorrhoeae (2)
- Translational research (2)
- cancer (2)
- deadwood enrichment (2)
- gene regulation (2)
- management (2)
- next generation sequencing (2)
- reactive electrophilic species (2)
- remote sensing (2)
- salt stress (2)
- saproxylic beetles (2)
- survival (2)
- (classical and atypical) Werner syndrome (1)
- 12-oxo-phytodienoic acid (1)
- ABCG2 (1)
- ABL gene (1)
- ADHD (1)
- Abstimmbare Laser (1)
- Agent (1)
- Aging (1)
- Alpha therapy (1)
- Alzheimer's disease (1)
- Arthropod (1)
- Autoimmune diseases (1)
- B cell malignancies (1)
- B cells (1)
- BCOR (1)
- BCORL1 (1)
- BCR‐ABL (1)
- BETA-Diversität (1)
- BETA-Multifunktionalität (1)
- BRAF(V600E) mutation (1)
- Biodiversität (1)
- Biologie (1)
- Biomarker (1)
- Bone marrow transplantantation (1)
- Breast-tumors (1)
- COVID-19 (1)
- COX-2 (1)
- CXCR4 (1)
- Cancer (1)
- Cancer genetics (1)
- Cardiovascular risk factors (1)
- Cardiovascular risk prediction (1)
- Carotid intima-media thickness (CIMT) (1)
- Carotid segment (1)
- Carotid ultrasound (1)
- Chronic myeloid leukaemia (1)
- Cognitive control (1)
- DFB-Laser (1)
- EZH1 (1)
- EZH2 (1)
- EZH2 differentiation trichostatin (1)
- Exercise (1)
- Expression (1)
- Factor receptor (1)
- Forschungsstation Fabrikschleichach (1)
- GRAID (1)
- Graft-versus-leukemia (1)
- H3K27me3 (1)
- HLA-E matching (1)
- HSTC outcome (1)
- HUWE1 (1)
- Halbleiterlaser (1)
- Hippocampus (1)
- Human Physiome (1)
- Imatinib (1)
- Immunologie (1)
- In-vivo (1)
- Inhibitor (1)
- LASP1 (1)
- LND (1)
- LNE (1)
- Laserarray (1)
- Lymantria dispar (1)
- M1/M2 macrophages (1)
- MFM (1)
- MIZ1 (1)
- MYC (1)
- Medical research (1)
- Molecularly targeted therapy (1)
- N170 (1)
- NFATc1 (1)
- NHX1 (1)
- NaCl transport (1)
- Neurotrophic factors (1)
- Nude-mice (1)
- Organische Chemie (1)
- P100 (1)
- PTCL (1)
- Pou2af1 (1)
- Prediction (1)
- Regulatory-cells (1)
- Rheumatoid arthritis (1)
- Risk factors (1)
- Salt Overly Sensitive pathway (1)
- Selective attention (1)
- Sentinel-1 (1)
- Staphylococcus aureus (1)
- Suppression (1)
- T cell differentiation (1)
- T cells (1)
- T-cell non-Hodgkin's lymphomas (1)
- TH1-induced senescence (1)
- TH17 cells (1)
- Tissue (1)
- Tumor-necrosis-factor (1)
- VAL66MET polymorphism (1)
- Vascular plasticity (1)
- Waldökosystem (1)
- Working memory (1)
- abscisic acid (ABA) (1)
- accessibility (1)
- acquired thermotolerance (1)
- acquisition (1)
- activation (1)
- acute leukemia (AL) (1)
- acute myeloid leukemia (1)
- adhesion dynamics (1)
- adolescents (1)
- adrenal cancer (1)
- adrenocortical carcinoma (1)
- amino acid transporter (1)
- anaemia (1)
- aneurysmal subarachnoid haemorrhage (1)
- antibodies (1)
- apolipoprotein-E4 (1)
- arabidopsis-thaliana (1)
- arterial stiffening (1)
- assembly mechanisms (1)
- association (1)
- atherosclerosis (1)
- autotoxicity (1)
- bcl-2 associated athanogene protein 3 (1)
- beech forest (1)
- beetle (1)
- beta diversity (1)
- beta-multifunctionality (1)
- biodiversity (1)
- bipartite metabolism (1)
- bipolar disorder (1)
- bird communities (1)
- bisulfite pyrosequencing (1)
- body size (1)
- bohemian forest ecosystem (1)
- brain (1)
- brain computer interface (1)
- breakpoint (1)
- breast cancer (1)
- broadleaf tree species (1)
- calcification (1)
- calcium signaling (1)
- cancer-targeted IL-12 (1)
- canopy herbivory (1)
- carotid artery disease (1)
- cell death (1)
- children (1)
- chronic myelogenous leukemia (1)
- chronic myeloid leukemia (1)
- chronic phase (1)
- coatings (1)
- colorectal cancer (1)
- community‐weighted mean (1)
- conservation (1)
- containment (1)
- crowded housing (1)
- cytogenetic response (1)
- cytosolic pH (1)
- cytotoxic T cells (1)
- cytotoxicity (1)
- data pool (1)
- dead-wood enrichment (1)
- deadwood (1)
- defoliation severity (1)
- detoxification (1)
- dfb-laser (1)
- different imatinib dose regimens (1)
- differentiation (1)
- digestive system (1)
- disability (1)
- dispersal ability (1)
- dissection (1)
- distant metastases (1)
- diversity (1)
- drug discovery (1)
- early applied higher imatinib dosages (1)
- early respiratory-failure (1)
- elderly (1)
- environmental filtering (1)
- enzyme-linked immunoassays (1)
- epigenetics (1)
- epigenomic landscapes (1)
- epithelial cells (1)
- evidence‐based medicine (1)
- ex vivo expansion (1)
- extinction risk (1)
- fear conditioning (1)
- fire (1)
- focal adhesions (1)
- follicular T helper cells (1)
- force (1)
- forest (1)
- forest biodiversity (1)
- forest conservation (1)
- forest ecosystem science (1)
- forest management (1)
- forest physiognomy (1)
- forestry (1)
- functional traits (1)
- gene-expression (1)
- genome-wide association (1)
- geographic information science (1)
- germinal center (1)
- glycophyte Arabidopsis (1)
- guard cell (1)
- guidelines (1)
- gypsy moth (1)
- habitat heterogeneity (1)
- halophyte Thellungiella/Eutrema (1)
- health care service research (1)
- hearing impairment (1)
- heart (1)
- heart failure (1)
- heat shock response (1)
- heat stress (1)
- hematopoietic stem cell transplantation (HSCT) (1)
- host cells (1)
- human leukocyte antigen-E (HLA-E) (1)
- humanized mice (1)
- humoral immunity (1)
- hybrid messenger RNA (1)
- immune cells (1)
- immunocytokine (1)
- immunohistochemistry (1)
- immunotherapy (1)
- impact (1)
- in vivo polycomb (1)
- independence (1)
- insect decline (1)
- insect disturbance (1)
- integrative management strategy (1)
- intra-annual time-series (1)
- intracerebral haemorrhage (1)
- ion transport (1)
- isothiocyanates (1)
- jasmonates (1)
- kidneys (1)
- land sharing (1)
- land use (1)
- laser array (1)
- leaf response (1)
- learning (1)
- limited mobility (1)
- loss-of-function (1)
- lowland beech forests (1)
- lymph node dissection (1)
- lymphadenectomy (1)
- lymphocyte activation (1)
- machine learning (1)
- macrophages (1)
- major depressive disorder (1)
- managing big data (1)
- medial prefrontal cortex (mPFC) (1)
- medicine (1)
- memory B cells (1)
- memory consolidation and extinction (1)
- messenger RNA (1)
- meta-analysis (1)
- methylation array (1)
- migrants (1)
- migration (1)
- model (1)
- molecular subtypes (1)
- mood disorder (1)
- morphometry (1)
- muscular-dystrophy (1)
- mustard oil bomb (1)
- myopathy (1)
- natural disturbance (1)
- near-infrared spectroscopy (1)
- networks (1)
- neurotrophic factor gene (1)
- neutral processes (1)
- neutrophils (1)
- nilotinib (1)
- no correlation (1)
- older patients (1)
- osmotic effects (1)
- papillary (1)
- patient blood management (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical cancer (1)
- pediatric adrenocortical tumor (1)
- pharmacology (1)
- phytoprostanes (1)
- plant composition (1)
- plants (1)
- polymerase-chain-reaktion (1)
- polyneuropathy (1)
- posttranscriptional regulation (1)
- precursor cells (1)
- premature aging (1)
- prognostic factors (1)
- protein aggregation (1)
- psychiatry (1)
- radioiodine therapy (1)
- red blood cell transfusion (1)
- red lists (1)
- redox homeostasis (1)
- refugees (1)
- regional species pool (1)
- remote sensing‐enabled essential biodiversity variables (1)
- repositories (1)
- reproducible science (1)
- respiratory infection (1)
- restoration strategy (1)
- review (1)
- rhabdomyosarcoma (1)
- risk stratification (1)
- sRNA (1)
- saproxylic organisms (1)
- saproxylic species (1)
- seasonality (1)
- segmental progeria (1)
- semiconductor lasers (1)
- sequence variations (1)
- service infrastructure (1)
- shock response (1)
- signal transduction (1)
- skeletal myopathy (1)
- soil (1)
- species traits (1)
- species turnover (1)
- spiders (1)
- standards (1)
- stomata (1)
- stress (1)
- sulforaphane (1)
- sun exposure (1)
- surgery (1)
- tension (1)
- therapy (1)
- thermotolerance (1)
- time series (1)
- tissue morphogenesis (1)
- traction (1)
- transcranial magnetic stimulation (TMS) (1)
- transcription deficiency (1)
- transcripts (1)
- transplantation states genes (1)
- transposable elements (1)
- treatment response (1)
- trophic position (1)
- tumor heterogeneity (1)
- tumor-infiltrating lymphocytes (1)
- tunable laser (1)
- ubiquitination (1)
- unfolded protein response (1)
- verbal fluency task (1)
- windthrow (1)
- wood‐inhabiting fungi (1)
- β-diversity (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (20)
- Medizinische Klinik und Poliklinik II (9)
- Pathologisches Institut (7)
- Julius-von-Sachs-Institut für Biowissenschaften (6)
- Medizinische Klinik und Poliklinik I (5)
- Institut für Humangenetik (4)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (4)
- Institut für Geographie und Geologie (3)
- Institut für Klinische Epidemiologie und Biometrie (3)
- Institut für Molekulare Infektionsbiologie (3)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 229289 (1)
- 288566 (1)
- 834709 (1)
- ZAM 5-85018031 (1)
Functional versus morphological assessment of vascular age in patients with coronary heart disease
(2021)
Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VA(PWVao) in 68% of patients; for VA\(_{AIao}\) in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VA\(_{total-cIMT}\) accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.
The enrichment of deadwood is essential for the conservation of saproxylic biodiversity in managed forests. However, existing strategies focus on a cost‐intensive increase of deadwood amount, while largely neglecting increasing deadwood diversity.
Deadwood objects, that is logs and branches, from six tree species were experimentally sun exposed, canopy shaded and artificially shaded for 4 years, after which the alpha‐, beta‐ and gamma‐diversity of saproxylic beetles, wood‐inhabiting fungi and spiders were analysed. Analyses of beta‐diversity included the spatial distance between exposed deadwood objects. A random‐drawing procedure was used to identify the combination of tree species and sun exposure that yielded the highest gamma‐diversity at a minimum of exposed deadwood amount.
In sun‐exposed plots, species numbers in logs were higher than in shaded plots for all taxa, while in branches we observed the opposite for saproxylic beetles. Tree species affected the species numbers only of saproxylic beetles and wood‐inhabiting fungi. The beta‐diversity of saproxylic beetles and wood‐inhabiting fungi among logs was influenced by sun exposure and tree species, but beta‐diversity of spiders by sun exposure only. For all saproxylic taxa recorded in logs, differences between communities increased with increasing spatial distance.
A combination of canopy‐shaded Carpinus logs and sun‐exposed Populus logs resulted in the highest species numbers of all investigated saproxylic taxa among all possible combinations of tree species and sun‐exposure treatments.
Synthesis and applications. We recommend incorporating the enrichment of different tree species and particularly the variation in sun exposure into existing strategies of deadwood enrichment. Based on the results of our study, we suggest to combine the logs of softwood broadleaf tree species (e.g. Carpinus, Populus), hardwood broadleaf tree species (e.g. Quercus) and coniferous tree species (e.g. Pinus) under different conditions of sun exposure and distribute them spatially in a landscape to maximize the beneficial effects on overall diversity.
Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different HK4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.
The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95%=0.48–0.83, P=0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50% vs. 18%, P=0.005; HR=0.40, CI 95%=0.22–0.72, P=0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post–transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs.
Introduction:
Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting.
Methods:
Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results:
A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm)
Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 757% (mean +/- SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed forest unlogged maintains 73 +/- 12% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups. Salvage logging has become a common practice to gain economic returns from naturally disturbed forests, but it could have considerable negative effects on biodiversity. Here the authors use a recently developed statistical method to estimate that ca. 75% of the naturally disturbed forest should be left unlogged to maintain 90% of the species unique to the area.
Small bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in a very few cases has the role in metabolism been demonstrated. Here, we performed a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR_162 and NgncR_163 (NgncR_162/163) and their impact on the metabolism of Neisseria gonorrhoeae. These sRNAs have been reported to control genes of the citric acid and methylcitric acid cycles by posttranscriptional negative regulation. By transcriptome analysis, we now expand the NgncR_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR_162/163 targets are mostly involved in transport processes, especially in the uptake of glycine, phenylalanine, and branched-chain amino acids. NgncR_162/163 also play key roles in the control of serine-glycine metabolism and, hence, probably affect biosyntheses of nucleotides, vitamins, and other amino acids via the supply of one-carbon (C\(_1\)) units. Indeed, these roles were confirmed by metabolomics and metabolic flux analysis, which revealed a bipartite metabolic network with glucose degradation for the supply of anabolic pathways and the usage of amino acids via the citric acid cycle for energy metabolism. Thus, by combined deep RNA sequencing (RNA-seq) and metabolomics, we significantly extended the regulon of NgncR_162/163 and demonstrated the role of NgncR_162/163 in the regulation of central metabolic pathways of the gonococcus.
The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6
(2016)
Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4\(^+\) T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses.
Background
Breast cancer (BC), which is most common in elderly women, requires a multidisciplinary and continuous approach to care. With demographic changes, the number of patients with chronic diseases such as BC will increase. This trend will especially hit rural areas, where the majority of the elderly live, in terms of comprehensive health care.
Methods
Accessibility to several cancer facilities in Bavaria, Germany, was analyzed with a geographic information system. Facilities were identified from the national BC guideline and from 31 participants in a proof‐of‐concept study from the Breast Cancer Care for Patients With Metastatic Disease registry. The timeframe for accessibility was defined as 30 or 60 minutes for all population points. The collection of address information was performed with different sources (eg, a physician registry). Routine data from the German Census 2011 and the population‐based Cancer Registry of Bavaria were linked at the district level.
Results
Females from urban areas (n = 2,938,991 [ie, total of females living in urban areas]) had a higher chance for predefined accessibility to the majority of analyzed facilities in comparison with females from rural areas (n = 3,385,813 [ie, total number of females living in rural areas]) with an odds ratio (OR) of 9.0 for cancer information counselling, an OR of 17.2 for a university hospital, and an OR of 7.2 for a psycho‐oncologist. For (inpatient) rehabilitation centers (OR, 0.2) and genetic counselling (OR, 0.3), women from urban areas had lower odds of accessibility within 30 or 60 minutes.
Conclusions
Disparities in accessibility between rural and urban areas exist in Bavaria. The identification of underserved areas can help to inform policymakers about disparities in comprehensive health care. Future strategies are needed to deliver high‐quality health care to all inhabitants, regardless of residence.
Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement.
Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms.
Results: We identified 14 heterozygous mutations (diagnostic yield of 37%), among them the novel p. Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p. Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29%).
Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim.