Genotypic and Phenotypic Analysis in Chinese Cohort With Autosomal Recessive Osteogenesis Imperfecta

This study recruited a Chinese cohort of 74 AR-OI families, aiming to establish the mutation spectrum and to examine the genotypic and phenotypic correlation. We identified 82 variants including 25 novel variants and 57 HGMD reported variants in these AR-OI patients, using whole exome sequencing/panel sequencing combined with Sanger sequencing. Pathogenic mutations were found at WNT1 (n = 30, 40.54%), SERPINF1 (n = 22, 29.73%), FKBP10 (n = 10, 13.51%), CRTAP (n = 3, 4.05%), P3H1 (n = 3, 4.05%), SERPINH1 (n = 2, 2.70%), SEC24D (n = 3, 4.05%), and PLOD2 (n = 1, 1.35%) respectively. Thus, WNT1 represents the most frequent pathogenic gene of AR-OI in Chinese population. The most common clinical manifestations of AR-OI patients include walking problem (72.86%), scoliosis (65.28%) and frequent fractures (fractures ≥2/year) (54.05%). Interestingly, ptosis represents a unique phenotype of patients carrying WNT1 variants, and it was rare in patients harboring other pathogenic genes. Our study expanded the mutation spectrum of AR-OI and enriched the knowledge of genotypic and phenotypic correlation in Chinese cohort with AR-OI.
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

Related Links:

ConclusionRespiratory symptoms negatively impact both psychosocial wellbeing in the OI population and limit daily physical activity. These limitations occur irrespective of their OI type, age, stature, or scoliosis and reflect the dramatic impact of respiratory status on quality of life for people with OI. Future studies should examine the etiology of respiratory insufficiency in this population so guidelines for management can be established.
Source: Archives of Orthopaedic and Trauma Surgery - Category: Orthopaedics Source Type: research
CORR Insights®: Cardiopulmonary Status in Adults with Osteogenesis Imperfecta: Intrinsic Lung Disease May Contribute More Than Scoliosis. Clin Orthop Relat Res. 2020 Sep 10;: Authors: Gerdhem P PMID: 32925237 [PubMed - as supplied by publisher]
Source: Clinical Orthopaedics and Related Research - Category: Orthopaedics Authors: Tags: Clin Orthop Relat Res Source Type: research
Abstract BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of collagen-related disorders characterized by osteopenia, bone fractures, spine deformities, and nonskeletal complications. Cardiopulmonary complications are the major cause of morbidity and mortality in adults with OI. The cause of such problems was often attributed solely to the presence of large scoliosis curves affecting pulmonary function and, indirectly, cardiovascular health. However, recent studies suggest this may not be the case. Therefore, determining the relationships and causative agents of cardiopulmonary problems in patients...
Source: Clinical Orthopaedics and Related Research - Category: Orthopaedics Authors: Tags: Clin Orthop Relat Res Source Type: research
Conclusion: The dramatic difference between the phenotypes of these 2 cases is significant because it is the largest known variability of phenotypic presentation in siblings. Previous cases of siblings with differing presentations at birth have been reported, but the extent of these differences is not as extreme as in our cases. Because Bruck syndrome presents similarly to osteogenesis imperfecta and could be clinically mistaken for a form of osteogenesis imperfecta if contractures are minimal, a reasonable focus for research efforts is the development of genetic diagnostic protocols for osteogenesis imperfecta with the go...
Source: Ochsner Journal - Category: General Medicine Tags: Ochsner J Source Type: research
In conclusion, our findings provided additional evidence of involvement of homozygous sequence variants in the SP7, SERPINF1, SPARC and WNT1 genes causing severe OI. It also highlights the importance of extensive genetic investigations to search for the culprit gene in each case of skeletal deformity. PMID: 32413570 [PubMed - as supplied by publisher]
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
This study reports the eighth child with OI and the homozygous mutation in COL1A2; and the first two individuals with the heterozygous p.Gly337Ser mutation in COL1A2 causing an isolated DI without OI. PMID: 32081708 [PubMed - as supplied by publisher]
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
Background: Osteogenesis imperfecta (OI) is an uncommon disorder frequently associated with spinal deformity. Relatively little is known about the effect this disorder has on the outcomes of spinal fusion for spinal deformity. The purpose of this study was to evaluate the differences in treatment and outcomes of this unique patient population. Methods: The nationwide HCUP Kids’ Inpatient Database (KID) from 2000 to 2012 was queried to identify patients with OI who underwent spinal fusion surgery for treatment of scoliosis. Demographic variables were obtained along with length of stay, mortality, length of fusion...
Source: Current Orthopaedic Practice - Category: Orthopaedics Tags: Original Research Source Type: research
Study Design. Retrospective clinical study of individuals with osteogenesis imperfecta (OI). Objective. To assess the relationship between severity of scoliosis and pulmonary function, and to assess the relationship between restrictive lung disease and self-reported quality of life in individuals with OI. Summary of Background Data. OI is a heritable connective tissue disorder characterized by osteopenia and a predisposition to fracture. Respiratory insufficiency is a leading cause of mortality. Literature on pulmonary function in this population has shown a negative correlation between percent-predicted vital capa...
Source: Spine - Category: Orthopaedics Tags: DEFORMITY Source Type: research
We describe the management of a pregnant patient with osteogenesis imperfecta with a history of numerous fractures, severe scoliosis, and anticipated difficult airway. Her pregnancy was complicated by progressive shortness of breath and a fetal diagnosis of osteogenesis imperfecta. Spine anatomy precluded neuraxial anesthesia. Cesarean delivery was performed under general anesthesia at 34 weeks. Immediately after awake fiberoptic intubation and induction of general anesthesia, capnography waveform was lost with rapid profound oxygen desaturation. A supraglottic airway device was placed, oxygenation maintained with supraglo...
Source: A&A Case Reports - Category: Anesthesiology Tags: Case Reports Source Type: research
Conclusion: For OI children, symptoms suggestive of obstructive sleep disorders should be searched for systematically, especially when autonomy is compromised, body mass index is high, trunk deformations are identified, and in case of severe type of OI.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Sleep and control of breathing Source Type: research
More News: Back Curves | China Health | Genetics | Orthopaedics | Osteogenesis Imperfecta (brittle bone disease) | Scoliosis | Study