Genetic analysis of osteogenesis imperfecta in the Palestinian population: molecular screening of 49 affected families

ConclusionThis is the first genetic screening of an OI cohort from the Palestinian population. Our data are important for genetic counseling of OI patients and families in highly consanguineous populations. In 41 Palestinian families with osteogensis imperfecta (OI), we identified 28 different mutations in nine OI genes, of which 11 mutations were novel. In eight remaining probands no mutation was found suggesting further genetic heterogeneity in OI. In contrast to the high frequency of the AD forms caused by defects in the structure or quantity of type I collagen in nonconsanguineous populations, AR forms of OI are expected to be more common in highly consanguineous populations.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: Original Article Source Type: research

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Cell-based therapies using mesenchymal stem/stromal cells (MSCs) have been extensively investigated both in preclinical and clinical settings. Because of their multipotency, MSCs have initially been expected to regenerate tissues by differentiating into native tissue cells. However, accumulating evidence suggests that the observed clinical benefits are largely from the trophic effects of MSCs. In pilot studies, systemic infusion of MSCs has been shown to clinically improve patients with osteogenesis imperfecta and hypophosphatasia even though donor cell engraftment was minimal, suggesting that the trophic effects of MSCs l...
Source: Techniques in Orthopaedics - Category: Orthopaedics Tags: Symposium Source Type: research
Purpose of review The purpose of this review is to outline the current understanding of the molecular mechanisms and natural history of osteogenesis imperfecta, and to describe the development of new treatments for this disorder. Recent findings The introduction of next-generation sequencing technology has led to better understanding of the genetic cause of osteogenesis imperfecta and enabled cost-effective and timely diagnosis via expanded gene panels and exome or genome sequencing. Clinically, despite genetic heterogeneity, different forms of osteogenesis imperfecta share similar features that include connective tis...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: GENETICS: Edited by Nathaniel H. Robin Source Type: research
ABSTRACTSclerostin antibody (Scl ‐Ab) is an anabolic bone agent that has been shown to increase bone mass in clinical trials of adult diseases of low bone mass, such as osteoporosis and osteogenesis imperfecta (OI). Its use to decrease bone fragility in pediatric OI has shown efficacy in several growing mouse models, suggesting t ranslational potential to pediatric disorders of low bone mass. However, the effects of pharmacologic inhibition of sclerostin during periods of rapid growth and development have not yet been described with respect to the cranium, where lifelong deficiency of functioning sclerostin leads to patt...
Source: Journal of Bone and Mineral Research - Category: Orthopaedics Authors: Tags: Original Article Source Type: research
Prostanoids (PNs), which consist of prostaglandin (PG) D2, PGE2, PGF2 α, PGI2, and thromboxane (TX)A2, are biosynthesized from arachidonic acid under the action of cyclooxygenases [1]. PNs play an important role in various physiological functions, such as vascular vasodilation/constriction [2], platelet aggregation [3] and pain perception [4]. Conversely, it has been reported that the abnormality of PN expression contributes to the onset or progression of many diseases such as asthma [5], headache [6], osteogenesis imperfecta [7], and inflammation-related diseases [8].
Source: Prostaglandins, Leukotrienes and Essential Fatty Acids - Category: Biomedical Science Authors: Source Type: research
Osteogenesis imperfecta (OI) is characterized by brittle bones, premature hearing loss, blue sclera, dental abnormalities, and short stature. Maxillofacial pathology is marked in many OI patients and includes a high incidence of class III malocclusion secondary to a retrusive maxilla relative to both the mandible and cranial base. Review of literature shows that most of the orthognathic surgeries performed in the setting of OI are double jaw surgeries, in the form of maxillary advancement and mandibular setback. However, severe maxillary hypoplasia is usually not correctable with single-stage maxillary advancement. Distra...
Source: Journal of Craniofacial Surgery - Category: Surgery Tags: Clinical Studies Source Type: research
Publication date: Available online 25 October 2019Source: Stem Cell ResearchAuthor(s): Bo-Young Kim, Jung Min Ko, Mi-hyun Park, Soo Kyung KooAbstractOsteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones. OI type I is the most common and usually the mildest form. We generated human induced pluripotent stem cells (hiPSCs), KSCBi006-A, from the peripheral blood mononuclear cells of a patient with OI type I using the Sendai virus delivery method. The generated hiPSCs retained the disease-causing DNA mutation (COL1A1, c.3162delT) and showed a normal karyotype. KSCBi006-A also has pluripotency and the...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
CONCLUSIONS: Osteogenesis imperfecta patients with haploinsufficient mutations had higher percentage of anisotropic collagen fibers alignment compared to other patient groups; all patients had a lower percentage of anisotropic samples compared to healthy controls. This correlated with higher average stiffness in the control group. Glycosaminoglycan content was lower in the control and haploinsufficient groups. In cells with PLOD1 mutations, there were no differences in PLOD2 expression. This proof of concept study was able to show differences in collagen fiber orientation between different patient groups which can potentia...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
ConclusionWe identified pathogenic mutations in 81% of our Japanese patients with OI. Most mutations were located onCOL1A1 andCOL1A2. This study revealed that glycine substitutions onCOL1A1 resulted in the severe phenotype among Japanese patients with OI.
Source: Osteoporosis International - Category: Orthopaedics Source Type: research
Publication date: Available online 22 October 2019Source: Journal of Advanced ResearchAuthor(s): Juan A. Sanchis-Gimeno, Stephanie Lois-Zlolniski, José María González-Ruiz, Carlos A. Palancar, Nicole Torres-Tamayo, Daniel García-Martínez, Luis Aparicio, Marcelino Perez-Bermejo, Esther Blanco-Perez, Federico Mata-Escolano, Susanna Llidó, Isabel Torres-Sanchez, Francisco García-Río, Markus BastirAbstractThe aim of the present study was to test the hypothesis that ribs shape changes in patients with OI are more relevant for respiratory function than thoracic spine shape....
Source: Journal of Advanced Research - Category: Research Source Type: research
In conclusion, the novel de novo heterozygous p.G511C mutation in COL1A2 and the heterozygous pathogenic p.R122W mutation in LHX4 were demonstrated in a patient with OI and CPHD. This study proposes that the mutations in two different genes should be sought in the patients with clinical features unable to be explained by a mutation in one gene.Graphical abstract
Source: Journal of Advanced Research - Category: Research Source Type: research
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