scholarly journals Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Joseph P. Pillion ◽  
David Vernick ◽  
Jay Shapiro
Keyword(s):  
Hearing Loss ◽  
Osteogenesis Imperfecta ◽  
Hearing Aids ◽  
Type I Collagen ◽  
Treatment Options ◽  
Type I ◽  
Collagen Triple Helix ◽  
Treatment Considerations ◽  
Heritable Disorder ◽  
Blue Sclerae

Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed.

scholarly journals Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

2021 ◽  
Vol 22 (1) ◽  
pp. 429
Author(s):  
Luca Bini ◽  
Domitille Schvartz ◽  
Chiara Carnemolla ◽  
Roberta Besio ◽  
Nadia Garibaldi ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Tandem Mass ◽  
Type Ii ◽  
Type Iii ◽  
Bioinformatic Tools ◽  
Proteomic Approach ◽  
Fibrillin 1 ◽  
Heritable Disorder

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

scholarly journals Structural Heterogeneity of Type I Collagen Triple Helix and Its Role in Osteogenesis Imperfecta

2007 ◽  
Vol 283 (8) ◽  
pp. 4787-4798 ◽  
Author(s):  
Elena Makareeva ◽  
Edward L. Mertz ◽  
Natalia V. Kuznetsova ◽  
Mary B. Sutter ◽  
Angela M. DeRidder ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Structural Heterogeneity ◽  
Type I ◽  
Collagen Triple Helix

scholarly journals Characterization of three osteogenesis imperfecta collagen α 1(I) glycine to serine mutations demonstrating a position-dependent gradient of phenotypic severity

1992 ◽  
Vol 288 (1) ◽  
pp. 131-135 ◽  
Author(s):  
J F Bateman ◽  
I Moeller ◽  
M Hannagan ◽  
D Chan ◽  
W G Cole
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Type I ◽  
Disruptive Effect ◽  
Collagen Triple Helix ◽  
C Terminus ◽  
Glycine Substitution ◽  
C And N

Type I collagen alpha 1(I) glycine to serine substitutions, resulting from G-to-A mutations, were defined in three cases of osteogenesis imperfecta (OI). The Gly substitutions displayed a gradient of phenotypic severity according to the location of the mutation in the collagen triple helix. The most C-terminal of these, Gly565 to Ser, led to the lethal perinatal (type II) form of OI, whereas the more N-terminal mutations, Gly415 and Gly352 to Ser, led to severe OI (type III/IV) and moderate OI (type IVB) respectively. These data support the notion that glycine substitutions towards the C-terminus of the alpha 1(I) or alpha 2(I) chains will be more clinically severe than those towards the N-terminus. This results from the more disruptive effect of the mutations at the C-terminus on helix initiation and C- and N-terminal helix directional propagation. This generalization must be modified by considering the nature of the glycine substitution and the surrounding amino acid sequence, since the helix is composed of subdomains of differing stability which will affect the ability of helix re-nucleation and propagation.

Hearing Loss in Finnish Adults with Osteogenesis Imperfecta: A Nationwide Survey

2002 ◽  
Vol 111 (10) ◽  
pp. 939-946 ◽  
Author(s):  
Kaija Kuurila ◽  
Reijo Johansson ◽  
Ilkka Kaitila ◽  
Reidar Grénman
Keyword(s):  
Hearing Loss ◽  
Osteogenesis Imperfecta ◽  
Clinical Features ◽  
Genetic Disorder ◽  
Nationwide Survey ◽  
Bone Fragility ◽  
Type I ◽  
Impaired Hearing ◽  
Hearing Ability ◽  
Blue Sclerae

Hearing loss, bone fragility, and blue sclerae are the principal clinical features in osteogenesis imperfecta (OI), a genetic disorder of connective tissue. In a nationwide search, an audiometric evaluation of 133 adult patients was performed. According to the criteria introduced by Sillence, type I was the most common form of OI. Of the patients with normal hearing on audiometry, 17.1% reported subjective hearing loss, and 19.1% of the patients with impaired hearing did not recognize it. On audiometry, 57.9% of the patients had hearing loss, which was progressive, often of mixed type, and mostly bilateral, and began in the second to fourth decades of life. The frequency or severity of the hearing loss was not correlated with any other clinical features of OI. Hearing loss is common, affecting patients with all types of OI. Subjective misjudgment of hearing ability supports the need for repeated audiometry in all OI patients. A baseline study at the age of 10 years followed by audiograms every third year thereafter is recommended.

Management of Multiple Mandibular Fractures in a Child with Osteogenesis Imperfecta Using Arch Bar Retained Thermoformed Splints: A Novel Technique

2016 ◽  
Vol 40 (4) ◽  
pp. 322-327 ◽  
Author(s):  
Kumar Nilesh ◽  
Ashwini Sawant ◽  
Swapnil Taur ◽  
M I Parkar
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Autosomal Dominant ◽  
Bone Fractures ◽  
Invasive Technique ◽  
Mandibular Fractures ◽  
Type I ◽  
Inherited Disorders ◽  
Arch Bar ◽  
Blue Sclerae

Osteogenesis Imperfecta (OI) is a heterogeneous group of autosomal dominant and recessive inherited disorders of type I collagen metabolism. Clinical features of OI include multiple bone fractures, muscle weakness, joint laxity, skeletal deformities, blue sclerae, hearing loss, and dentinogenesis imperfecta. This report presents a challenging case of multiple mandibular fractures in a five years old child with OI, which was successfully treated with a new, minimally invasive technique of closed reduction with arch bar retained thermoformed splint.

scholarly journals Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta

2021 ◽  
Vol 10 (14) ◽  
pp. 3141
Author(s):  
Hyerin Jung ◽  
Yeri Alice Rim ◽  
Narae Park ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Disease Modeling ◽  
Bone Fragility ◽  
Osteogenic Potential ◽  
Type I ◽  
Gene Correction ◽  
Col1a1 Gene ◽  
Collagen Formation

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of COL1A1 or COL1A2. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the COL1A1 gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the COL1A1 gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9.

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