Recessive osteogenesis imperfecta caused by missense mutations in SPARC

2015 ◽  
Author(s):  
Roberto Mendoza ◽  
Somayyeh Fahiminiya ◽  
Jacek Majewski ◽  
Martine Tetreault ◽  
Javad Nadaf ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Missense Mutations

scholarly journals Recessive Osteogenesis Imperfecta Caused by Missense Mutations in SPARC

2015 ◽  
Vol 96 (6) ◽  
pp. 979-985 ◽  
Author(s):  
Roberto Mendoza-Londono ◽  
Somayyeh Fahiminiya ◽  
Jacek Majewski ◽  
Martine Tétreault ◽  
Javad Nadaf ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Missense Mutations

scholarly journals PHENOTYPIC CHARACTERISTICS IN OSTEOGENESIS IMPERFECTA PATIENTS

2019 ◽  
Vol 21 (5) ◽  
pp. 266-271
Author(s):  
Olga N. Ignatovich
Keyword(s):  
Osteogenesis Imperfecta ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Clinical Manifestations ◽  
Hereditary Disease ◽  
Type I ◽  
Missense Mutations ◽  
Phenotypic Characteristics ◽  
Molecular Genetic Study ◽  
Collagen Genes

Osteogenesis imperfecta (OI) is a heterogeneous hereditary disease characterized by low bone density and frequent fractures. There are presented data of molecular genetic study and examination of 45 children with a clinically established diagnosis of types I, III and IV. The aim of investigation. To study the variety of clinical manifestations in OI children with and to compare with the identified genetic mutations in the genes COL1A1 and COL1A2. Materials and methods. The data of molecular genetic research and evaluation of clinical manifestations of 45 children with diagnosis OI of types I, III and IV is presented. Results. In the study, mutations in the genes COL1A1 and COL1A2 were detected in 43 (95.6%). The most of the mutations (74,4%) were found to be localized in the gene COL1A1 (n=32), smaller (25.6%) - in the gene COL1A2 (n=11). Glycine-to-serine substitutions in the Gly-X-Y triplet are the most frequent type of mutation among missense mutations. In children with type I qualitative mutations were found to be less common than in types III and IV (representing clinically severe and moderate, respectively). Conclusion. Majority of OI patients had mutations in the collagen genes. The most frequent mutation was the missense mutation, the most often detected in children with OI type III having a severe course, leading to a qualitative violation of collagen.

scholarly journals Osteogenesis Imperfecta Missense Mutations in Collagen: Structural Consequences of a Glycine to Alanine Replacement at a Highly Charged Site

Biochemistry ◽  
2011 ◽  
Vol 50 (50) ◽  
pp. 10771-10780 ◽  
Author(s):  
Jianxi Xiao ◽  
Haiming Cheng ◽  
Teresita Silva ◽  
Jean Baum ◽  
Barbara Brodsky
Keyword(s):  
Osteogenesis Imperfecta ◽  
Missense Mutations ◽  
Charged Site

Structural Consequences of Glycine Missense Mutations in Osteogenesis Imperfecta

2014 ◽  
pp. 115-124
Author(s):  
Barbara Brodsky ◽  
Anton Persikov
Keyword(s):  
Osteogenesis Imperfecta ◽  
Missense Mutations

scholarly journals Omics Profiling of S2P Mutant Fibroblasts as a Mean to Unravel the Pathomechanism and Molecular Signatures of X-Linked MBTPS2 Osteogenesis Imperfecta

2021 ◽  
Vol 12 ◽  
Author(s):  
Pei Jin Lim ◽  
Severin Marfurt ◽  
Uschi Lindert ◽  
Lennart Opitz ◽  
Timothée Ndarugendamwo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Osteogenesis Imperfecta ◽  
Er Stress ◽  
Bone Development ◽  
Differentially Expressed ◽  
Single Amino Acid ◽  
Missense Mutations ◽  
Cartilage Development ◽  
Molecular Features

Osteogenesis imperfecta (OI) is an inherited skeletal dysplasia characterized by low bone density, bone fragility and recurrent fractures. The characterization of its heterogeneous genetic basis has allowed the identification of novel players in bone development. In 2016, we described the first X-linked recessive form of OI caused by hemizygous MBTPS2 missense variants resulting in moderate to severe phenotypes. MBTPS2 encodes site-2 protease (S2P), which activates transcription factors involved in bone (OASIS) and cartilage development (BBF2H7), ER stress response (ATF6) and lipid metabolism (SREBP) via regulated intramembrane proteolysis. In times of ER stress or sterol deficiency, the aforementioned transcription factors are sequentially cleaved by site-1 protease (S1P) and S2P. Their N-terminal fragments shuttle to the nucleus to activate gene transcription. Intriguingly, missense mutations at other positions of MBTPS2 cause the dermatological spectrum condition Ichthyosis Follicularis, Atrichia and Photophobia (IFAP) and Keratosis Follicularis Spinulosa Decalvans (KFSD) without clinical overlap with OI despite the proximity of some of the pathogenic variants. To understand how single amino acid substitutions in S2P can lead to non-overlapping phenotypes, we aimed to compare the molecular features of MBTPS2-OI and MBTPS2-IFAP/KFSD, with the ultimate goal to unravel the pathomechanisms underlying MBTPS2-OI. RNA-sequencing-based transcriptome profiling of primary skin fibroblasts from healthy controls (n = 4), MBTPS2-OI (n = 3), and MBTPS2-IFAP/KFSD (n = 2) patients was performed to identify genes that are differentially expressed in MBTPS2-OI and MBTPS2-IFAP/KFSD individuals compared to controls. We observed that SREBP-dependent genes are more downregulated in OI than in IFAP/KFSD. This is coupled to alterations in the relative abundance of fatty acids in MBTPS2-OI fibroblasts in vitro, while no consistent alterations in the sterol profile were observed. Few OASIS-dependent genes are suppressed in MBTPS2-OI, while BBF2H7- and ATF6-dependent genes are comparable between OI and IFAP/KFSD patients and control fibroblasts. Importantly, we identified genes involved in cartilage physiology that are differentially expressed in MBTPS2-OI but not in MBTPS2-IFAP/KFSD fibroblasts. In conclusion, our data provide clues to how pathogenic MBTPS2 mutations cause skeletal deformities via altered fatty acid metabolism or cartilage development that may affect bone development, mineralization and endochondral ossification.

Abstract #1235: Osteogenesis Imperfecta: Differences in Fracture Rates Between Responders and Non-Respoders Following Bisphosphonate Therapy

2015 ◽  
Vol 21 ◽  
pp. 293
Author(s):  
Jay Shapiro ◽  
Evelise Brizola ◽  
Aditi Kantipuly
Keyword(s):  
Osteogenesis Imperfecta ◽  
Bisphosphonate Therapy

Abstract #510: Transient Osteoporosis of the Right Hip in a Patient with Osteogenesis Imperfecta

2017 ◽  
Vol 23 ◽  
pp. 104-105
Author(s):  
William Moore ◽  
Amy Warriner
Keyword(s):  
Osteogenesis Imperfecta ◽  
Transient Osteoporosis ◽  
The Right

Osteogenesis imperfecta: the impact of therapy with teriparatide

IBMS BoneKEy ◽  
2014 ◽  
Vol 11 ◽  
pp. 626
Keyword(s):  
Osteogenesis Imperfecta ◽  
The Impact

Bone Healing in Children With Osteogenesis Imperfecta Treated With Bisphosphonates

2006 ◽  
Vol 2006 ◽  
pp. 185-186
Author(s):  
A.E. Oestreich
Keyword(s):  
Osteogenesis Imperfecta ◽  
Bone Healing
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