Publications by authors named "Mari Muurinen"
Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare skeletal dysplasia characterized primarily by progressive osteolysis, particularly affecting the carpal and tarsal bones, accompanied by osteoporosis. In addition, it features subcutaneous nodules on the palms and soles, along with the progressive onset of arthropathy, encompassing joint contractures, pain, swelling and stiffness. It is caused by a deficiency of the Matrix Metalloproteinase-2 (MMP2).
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- Researchers studied mutations in a gene that affects a key protein involved in cell signaling, which is linked to severe health issues like impaired immunity in patients.
- The mutations were found to disrupt normal cell behavior by promoting excessive cell growth and responses to immune signals, specifically T cell receptor stimulation.
- The mutant protein was shown to interfere with a regulatory protein, leading to heightened activity of important signaling pathways that contribute to cell growth and survival.
Polydactyly is a rare autosomal dominant or recessive appendicular patterning defect of the hands and feet, phenotypically characterized by the duplication of digits. Postaxial polydactyly (PAP) is the most common form and includes two main types: PAP type A (PAPA) and PAP type B (PAPB). Type A involves a well-established extra digit articulated with the fifth or sixth metacarpal, while type B presents a rudimentary or poorly developed superfluous digit.
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- The primary molecular cause involves hypomethylation in the 11p15.5 region, but 40% of cases have an unknown cause.
- A new pathogenic variant related to the IGF2 gene has been discovered in a 16-year-old SRS patient, indicating that targeted exome sequencing is effective for diagnosing patients who don't show results from standard tests.
Article Synopsis
- Mosaicism involves having genetically distinct cells in the body, which can complicate diagnosis due to subtle symptoms and detection challenges.
- In a study using whole-genome sequencing, researchers identified mosaic genetic deletions in two patients with skeletal disorders: a 7-nucleotide frameshift in a female with osteopathia striata and a 3710-basepair deletion in a male with cleidocranial dysplasia.
- The findings suggest that mosaicism is an important factor in unexplained skeletal dysplasia cases and should be investigated using advanced detection techniques.
Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3).
View Article and Find Full Text PDFIn the last decade, the widespread use of massively parallel sequencing has considerably boosted the number of novel gene discoveries in monogenic skeletal diseases with short stature. Defects in genes playing a role in the maintenance and function of the growth plate, the site of longitudinal bone growth, are a well-known cause of skeletal diseases with short stature. However, several genes involved in extracellular matrix composition or maintenance as well as genes partaking in various biological processes have also been characterized.
View Article and Find Full Text PDFBackground: CCAAT enhancer-binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.
Objective: The aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.
Silver-Russell syndrome (SRS) is a growth retardation syndrome in which loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy for chromosome 7 [UPD(7)mat] explain 20-60% and 10% of the syndrome, respectively. To search for a molecular cause for the remaining SRS cases, and to find a possible common epigenetic change, we studied DNA methylation pattern of more than 450 000 CpG sites in 44 SRS patients. Common to all three SRS subgroups, we found a hypomethylated region at the promoter region of HOXA4 in 55% of the patients.
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- DNA methylation plays a crucial role in genomic imprinting, with differentially methylated regions (DMRs) found near imprinted genes that are expressed from only one parental allele.
- Maternal uniparental disomy for chromosome 7 (matUPD7) leads to Silver-Russell syndrome (SRS), which causes growth issues, but no specific gene has been linked to SRS until now.
- A study on matUPD7 patients identified ten novel DMRs, including two associated with potential imprinted genes, HOXA4 and GLI3, highlighting the first comprehensive mapping of parent-of-origin specific DMRs on chromosome 7 and suggesting several new imprinted sites.
Introduction: People born preterm at very low birth weight (VLBW, ≤1500g) have higher rates of risk factors for adult-onset diseases, including cardiovascular diseases and type 2 diabetes. These risks may be mediated through epigenetic modification of genes that are critical to normal growth and development.
Methods: We measured the methylation level of an imprinted insulin-like-growth-factor 2 (IGF2) locus (IGF2/H19) in young adults born preterm at VLBW and in their peers born at term.