A5035327021- Metabolism and Genetic Disorders
- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- Glycogen Storage Diseases and Myoclonus
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Dermatological and Skeletal Disorders
- Genomic variations and chromosomal abnormalities
- Diet and metabolism studies
- Genetic Neurodegenerative Diseases
- Connective tissue disorders research
- Neurological and metabolic disorders
- Nuclear Structure and Function
- Neurogenetic and Muscular Disorders Research
- Diabetes and associated disorders
- Renal Diseases and Glomerulopathies
- Growth Hormone and Insulin-like Growth Factors
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Neurological disorders and treatments
- Cardiomyopathy and Myosin Studies
- Neuroendocrine Tumor Research Advances
- Peroxisome Proliferator-Activated Receptors
- Genetic and Kidney Cyst Diseases
- Neonatal Health and Biochemistry
University of Helsinki
2015-2024
Helsinki University Hospital
2015-2024
Helsinki Children's Hospital
2000-2020
Institute of Genetics
2018
Children's Hospital
2010-2013
University of Bergen
1998
The salivary α-amylase locus (AMY1) is located in a highly polymorphic multi allelic copy number variable chromosomal region. A recent report identified an association between AMY1 numbers and BMI common obesity. present study investigated the relationship number, serum amylase childhood-onset obesity.Sixty-one subjects with history of obesity (mean age 19.1 years, 54% males) 71 matched controls (19.8 yrs, 45% were included. All anthropometric measures greater obese; their mean was 40 kg/m2...
Context: The H19 imprinting control region (ICR), located on chromosome 11p15.5, has been reported hypomethylated in 20–65% of Silver-Russell syndrome (SRS) patients. Objective: We investigated the methylation status 11p15.5 ICRs SRS patients and children born small for gestational age (SGA) to clarify relationship between phenotype status. Methods: performed screens KCNQ1OT1 42 patients, including seven maternal uniparental disomy 7 90 SGA without SRS. Clinical data were evaluated from...
Silver-Russell syndrome (SRS, OMIM 180860) features fetal and postnatal growth restriction variable dysmorphisms. Genetic epigenetic aberrations on chromosomes 7 11 are commonly found in SRS. However, a large fraction of SRS cases remain with unknown genetic aetiology.22 patients diagnosis (10 H19 hypomethylation 12 molecular aetiology) their parents were studied the Affymetrix 250K Sty microarray. Several analytical approaches used to identify genomic such as copy number changes (CNCs),...
Context: Observations in rodents suggest that osteocalcin (OC) participates glucose metabolism. Based on human studies, it remains unclear whether circulating OC is simply a bone turnover marker (BTM) or also mediator interactions between the skeleton and homeostasis. Objective: The objective of study was to determine responses BTMs, including OC, oral tolerance test (OGTT) case-control setting. Design Patients: Thirty-four normoglycemic young adults [mean age 19 y (SD 2.3)] with severe...
Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 a key component heterotrimeric protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients activating had clinical presentations that included impaired immunity. Mutant cell migration and augmented responses T receptor (TCR)...
Two Finnish cohorts, comprising 56 children with severe early-onset obesity (relative weight for height greater than or equal to +70% before age 10) and 252 morbidly obese adults (body mass index, ≥40 kg/m2), were screened melanocortin-4 receptor (MC4R) mutations. We identified a pathogenic mutation (S127L) in one child, causing obesity. describe the phenotype of this particular first time. also novel (I226T) polymorphism coding two new variations (−439delGC 1059C>T) outside region MC4R...
The aims of this study were to evaluate the efficacy and safety different doses growth hormone (GH) treatment in prepubertal short children born small-for-gestational-age (SGA). Forty-eight SGA from Sweden, Finland, Denmark Norway randomly allocated three groups: a control group 12 received no for 2 y, one was treated with GH at 0.1 IU/kg/d (n= 16), 0.2 20). In total 42 completed y follow-up, 24 groups 3 treatment. Their mean (SD) age start 4.69 (1.61) their height -3.16 (0.70) standard...
Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients and maternally inherited gingival fibromatosis. We report that from three unrelated families harbor either two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), KCNQ1, a gene previously implicated the long QT interval syndrome. Kcnq1 is expressed hypothalamic GHRH neurons pituitary...
Context: The hypothalamic circuit has an essential role in the regulation of appetite and energy expenditure. Pathogenic variants genes involved leptin–melanocortin pathway, including melanocortin-4-receptor (MC4R), have been associated with monogenic obesity. Objective: To determine rate spectrum rare melanocortin pathway or development patients severe early-onset obesity (height-adjusted weight >60% before age 10 years). Methods: We used a custom-made targeted exome sequencing panel to...
The aims of this study were to evaluate the efficacy and safety different doses growth hormone (GH) treatment in prepubertal short children born small‐for‐gestational‐age (SGA). Forty‐eight SGA from Sweden, Finland, Denmark Norway randomly allocated three groups: a control group 12 received no for 2 y, one was treated with GH at 0.1 IU/kg/d ( n = 16), 0.2 20). In total 42 completed y follow‐up, 24 groups 3 treatment. Their mean (SD) age start 4.69 (1.61) their height ‐3.16 (0.70) standard...
The aim was to evaluate whether the metabolic syndrome associates with other endocrinopathies observed after allogeneic stem cell transplantation (SCT) in childhood. Thirty-one SCT long-term survivors, transplanted for leukemia (n=26) or nonmalignant hematologic diseases (n=5) were evaluated by oral glucose tolerance test and assessment of serum lipids at a median age 15 (range 7 34) years. Hyperinsulinemia, hypertriglyceridemia, abdominal obesity required diagnosis syndrome. Growth hormone...
Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for metabolic syndrome. It caused by recessive mutations in the TRIM37 gene encoding peroxisomal protein ubiquitin-ligase activity. In this work, frequency pathology of malignant benign tumours were analysed national cohort 89 Finnish MUL patients aged 0.7-76 years. The subjects had radiological evaluation, histological immunohistocemical analyses on...
DNA methylation is a hallmark of genomic imprinting and differentially methylated regions (DMRs) are found near in imprinted genes. Imprinted genes expressed only from the maternal or paternal allele their normal balance can be disrupted by uniparental disomy (UPD), inheritance both chromosomes chromosome pair exclusively either mother father. Maternal UPD for 7 (matUPD7) results Silver-Russell syndrome (SRS) with typical features growth retardation, but no gene has been conclusively...
TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. depletion from tissue culture cells results supernumerary foci bearing the centriolar protein Centrin. Here, we characterize these assemblies (Cenpas) to uncover mechanism of action TRIM37. We find that atypical de novo assembly pathway can generate Cenpas act as microtubule-organizing centers (MTOCs), including patient cells. Correlative light electron microscopy...
Mulibrey nanism is a rare inherited disease characterized by growth failure and multiorgan manifestations, including constrictive pericarditis. Its long-term course, the results of pericardiectomy, details myocardial involvement have not been reported previously.We studied 49 patients (26 men) born before 1985 followed for up to 25 years. By 1999, (51%) had developed congestive heart (CHF), 19 (39%) undergone pericardiectomy pericarditis, 10 (22%) died cardiac causes, 5 (10%) noncardiac...
Epigenetic studies, such as the measurement of DNA methylation, are important in investigation syndromes influenced by imprinted genes. Quick and accurate quantification methylation at genes can be appreciable diagnostic aid.We first digested genomic with methylation-sensitive restriction enzymes used without digestion a control nonmethylated lambda an internal for efficiency. We then performed quantitative real-time PCR analyses 6 unique assays to investigate 4 imprinting regions on...
Mulibrey nanism is an autosomal recessive prenatal-onset growth disorder of unknown pathogenesis. The main clinical features are pre- and postnatal failure, characteristic dysmorphic craniofacial features, heart disease, hepatomegaly. Five truncating mutations in the TRIM37 gene have previously been reported patients. protein encodes a novel function. It contains tripartite motif (TRIM, also denoted RING-B-box-Coiled-coil or RBCC domain) TRAF (tumor necrosis factor-receptor associated...
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 caused loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family having both peroxisomal nuclear localization. We describe congenic Trim37 knock-out mouse (Trim37−/−) model MUL. Trim37−/− mice were viable...