GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    High frequency of tumours in Mulibrey nanism
    Wiley ; 2009
    In:  The Journal of Pathology Vol. 218, No. 2 ( 2009-06), p. 163-171
    Details
    In: The Journal of Pathology, Wiley, Vol. 218, No. 2 ( 2009-06), p. 163-171
    Abstract: Mulibrey nanism (MUL) is a monogenic disorder with prenatal‐onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin‐ligase activity. In this work, the frequency and pathology of malignant and benign tumours were analysed in a national cohort of 89 Finnish MUL patients aged 0.7–76 years. The subjects had a clinical and radiological evaluation, and histological and immunohistocemical analyses on specimens obtained from biopsy, surgery or autopsy, were performed. The results show that the MUL patients have disturbed architecture with ectopic tissues and a high frequency of both benign and malignant tumours detectable in several internal organs. A total of 210 tumorous lesions were detected in 66/89 patients (74%). Fifteen malignancies occurred in 13 patients (15%), seven of them in the kidney (five Wilms' tumours), three in the thyroid gland, two gynaecological cancers, one gastrointestinal carcinoid tumour, one neuropituitary Langerhans cell histiocytosis and one case of acute lymphoblastic leukaemia (ALL). Tumours detected by radiology in the liver and other organs mainly comprised strongly dilated blood vessels (peliosis), vascularized cysts and nodular lesions. The lesions showed strong expression of the endothelial cell markers CD34 and CD31 as well as the myocyte marker α‐smooth muscle actin (α‐SMA). Our findings show that MUL is associated with frequent malignant tumours and benign adenomatous and vascular lesions, as well as disturbed organ development. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 0022-3417 , 1096-9896
    URL: Issue
    URL: Article
    DOI: 10.1002/path.v218:2
    DOI: 10.1002/path.2538
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 1475280-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Renal findings in patients with Mulibrey nanism
    Springer Science and Business Media LLC ; 2017
    In:  Pediatric Nephrology Vol. 32, No. 9 ( 2017-9), p. 1531-1536
    Details
    In: Pediatric Nephrology, Springer Science and Business Media LLC, Vol. 32, No. 9 ( 2017-9), p. 1531-1536
    Type of Medium: Online Resource
    ISSN: 0931-041X , 1432-198X
    URL: Article
    DOI: 10.1007/s00467-017-3669-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1463004-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Liver pathology and biochemistry in patients with mutations in TRIM37 gene (Mulibrey nanism)
    Wiley ; 2022
    In:  Liver International Vol. 42, No. 6 ( 2022-06), p. 1369-1378
    Details
    In: Liver International, Wiley, Vol. 42, No. 6 ( 2022-06), p. 1369-1378
    Abstract: Mulibrey nanism (MUL) is a multiorgan disease caused by recessive mutations in the TRIM37 gene. Chronic heart failure and hepatopathy are major determinants of prognosis in MUL patients, which prompted us to study liver biochemistry and pathology in a national cohort of MUL patients. Methods Clinical, laboratory and imaging data were collected in a cross‐sectional survey and retrospectively from hospital records. Liver histology and immunohistochemistry for 10 biomarkers were assessed. Results Twenty‐one MUL patients (age 1–51 years) with tumour suspicion showed moderate congestion, steatosis and fibrosis in liver biopsies and marginally elevated levels of serum GGT, AST, ALT and AST to platelet ratio index (APRI) in 20%–66%. Similarly, GGT, AST, ALT and APRI levels were moderately elevated in 12%–69% of 17 MUL patients prior to pericardiectomy. In a cross‐sectional evaluation of 36 MUL outpatients, GGT, total bilirubin and galactose half‐life (Gal½) correlated with age ( r  = 0.45, p  = .017; r  = 0.512, p  = .007; r  = 0.44, p  = .03 respectively). The frequency of clearly abnormal serum values of 15 parameters analysed, however, was low even in patients with signs of restrictive cardiomyopathy. Transient elastography (TE) of the liver revealed elevated levels in 50% of patients with signs of heart failure and TE levels correlated with several biochemistry parameters. Biomarkers of fibrosis, sinusoidal capillarization and hepatocyte metaplasia showed increased expression in autopsy liver samples from 15 MUL patients. Conclusion Liver disease in MUL patients was characterized by sinusoidal dilatation, steatosis and fibrosis with individual progression to cirrhosis and moderate association of histology with cardiac function, liver biochemistry and elastography.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.v42.6
    DOI: 10.1111/liv.15213
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2124684-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Trim37 -deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism
    The Company of Biologists ; 2016
    In:  Biology Open Vol. 5, No. 5 ( 2016-05-15), p. 584-595
    Details
    In: Biology Open, The Company of Biologists, Vol. 5, No. 5 ( 2016-05-15), p. 584-595
    Abstract: Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37−/−) model for MUL. Trim37−/− mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37−/− mice as compared with wild-type. Both male and female Trim37−/− mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37−/− mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37−/− mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37−/− mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37−/− mice. The most consistently seen phenotypes in Trim37−/− mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37−/− mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis.
    Type of Medium: Online Resource
    ISSN: 2046-6390
    URL: Article
    DOI: 10.1242/bio.016246
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2016
    detail.hit.zdb_id: 2632264-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Testicular Failure and Male Infertility in the Monogenic Mulibrey Nanism Disorder
    The Endocrine Society ; 2011
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 96, No. 11 ( 2011-11), p. 3399-3407
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 96, No. 11 ( 2011-11), p. 3399-3407
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2011-1493
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2011
    detail.hit.zdb_id: 2026217-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Growth and Growth Hormone Therapy in Subjects With Mulibrey Nanism
    American Academy of Pediatrics (AAP) ; 2007
    In:  Pediatrics Vol. 120, No. 1 ( 2007-07-01), p. e102-e111
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 120, No. 1 ( 2007-07-01), p. e102-e111
    Abstract: OBJECTIVES. Mulibrey nanism is a monogenic disorder with prenatal-onset growth restriction, mild dysmorphic features, and a strong tendency for insulin resistance but no major neurologic handicap. Growth hormone therapy has been shown to promote short-term growth in children born small for gestational age, but the experience with long-term therapy is insufficient. Growth in patients with mulibrey nanism has not been analyzed previously in detail. METHODS. We evaluated the natural growth pattern and long-term impact of growth hormone treatment in the largest cohort of subjects with mulibrey nanism to date. The study included 72 living subjects followed up to 30 years. Thirty (18 female) were treated with recombinant human growth hormone for a median period of 5.7 years. Patients were reviewed at baseline and every 6 to 12 months during the therapy. Evaluation included assessment of height, weight, and pubertal status and laboratory analyses. Glucose metabolism was evaluated by oral glucose-tolerance test. RESULTS. The patients were born small for gestational age with immature craniofacial features. They experienced a continuous deceleration in height (median decrement of 1.1 SDS) and weight for height (median reduction of 17%) in infancy followed by an incomplete catch-up growth lasting up to school age. The final adult height averaged 136 cm in girls and 150 cm in boys. Growth hormone treatment improved the prepubertal growth but had only little impact on adult height (+5 cm). The treated subjects showed earlier bone maturation and growth arrest but not a significant increase in insulin resistance. On the contrary, the subjects who were treated with growth hormone were slimmer and had less metabolic syndrome as young adults. CONCLUSIONS. The patients with mulibrey nanism showed a distinct postnatal growth pattern. The growth hormone treatment was safe and induced a good short-term effect, but the impact on the adult height remained modest.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    URL: Article
    DOI: 10.1542/peds.2006-2686
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2007
    detail.hit.zdb_id: 1477004-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Genome-wide profiling of target genes for the systemic lupus erythematosus-associated transcription factors IRF5 and STAT4
    BMJ ; 2013
    In:  Annals of the Rheumatic Diseases Vol. 72, No. 1 ( 2013-01), p. 96-103
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 72, No. 1 ( 2013-01), p. 96-103
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2012-201364
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2013
    detail.hit.zdb_id: 1481557-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Insulin Resistance Syndrome in Subjects With Mutated RING Finger Protein TRIM37
    American Diabetes Association ; 2005
    In:  Diabetes Vol. 54, No. 12 ( 2005-12-01), p. 3577-3581
    Details
    In: Diabetes, American Diabetes Association, Vol. 54, No. 12 ( 2005-12-01), p. 3577-3581
    Abstract: We evaluated the glucose and lipid metabolism in 65 patients (aged 1.1–55 years) with mulibrey (muscle-liver-brain-eye) nanism (MUL), which is a monogenic disorder with prenatal-onset growth failure and typical clinical characteristics. MUL is caused by mutations in the TRIM37 gene, encoding a peroxisomal protein (TRIM37) with E3 ubiquitin-ligase activity. The subjects underwent clinical evaluation, abdominal ultrasonography, and laboratory measurements, including a 3-h oral glucose tolerance test. The results showed a dramatic change in glucose and lipid metabolism with age in MUL subjects. While the children had low fasting glucose and insulin levels, 90% of the adults had high fasting and postload insulin values (up to 1,450 mU/l). A 10-fold decrease in the fasting glucose-to-insulin ratio and a 4-fold decrease in whole-body insulin sensitivity index were observed. Insulin resistance, fatty liver, high serum leptin, hypertension, and acantosis nigricans were already evident in many slim prepubertal children. Half of the adults had type 2 diabetes, and an additional 42% showed impaired glucose tolerance. Seventy percent fulfilled the National Cholesterol Education Program criteria for metabolic syndrome. The peroxisomal targeting and the functional link of TRIM37 to the ubiquitin-proteosome pathway may provide novel clues to the development of metabolic syndrome.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/diabetes.54.12.3577
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2005
    detail.hit.zdb_id: 1501252-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Tissue expression of the mulibrey nanism-associated Trim37 protein in embryonic and adult mouse tissues
    Springer Science and Business Media LLC ; 2006
    In:  Histochemistry and Cell Biology Vol. 126, No. 3 ( 2006-8-15), p. 325-334
    Details
    In: Histochemistry and Cell Biology, Springer Science and Business Media LLC, Vol. 126, No. 3 ( 2006-8-15), p. 325-334
    Type of Medium: Online Resource
    ISSN: 0948-6143 , 1432-119X
    URL: Article
    DOI: 10.1007/s00418-006-0162-9
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 1398345-3
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...