Osteogenesis imperfecta (OI) is a heterogeneous disorder characterised by bone fragility. Herein, we report a case of OI diagnosed after subchondral insufficiency fracture (SIF) of bilateral femoral heads. A 37-year-old woman was referred to Saitama Medical University Hospital due to left hip pain without any trauma that lasted for 2 months. She was subsequently diagnosed with SIF of the left femoral head. After 3 months, she further developed SIF of the right hip without any trauma. Magnetic resonance imaging of the bilateral hips showed linear low-signal changes of the subchondral bone and bone marrow oedema of the femoral head on T2-weighted coronal and sagittal images, diagnosing of both SIFs. The bone mineral density was 0.851 g/cm2 (T-score, -1.3) at the lumbar spine, 0.578 g/cm2 (T-score, -1.9) at the right femoral neck, and 0.582 g/cm2 (T-score, -1.9) at the left femoral neck. Considering that the patient had multiple histories of fracture, blue sclera, and mild bilateral sensorineural hearing loss, she satisfied the diagnostic criteria for OI. Genetic testing revealed a mutation in COL1A1 (NM_000088.3, c.3806G>A: p. Trp1269*). After 7 months of conservative therapy, her symptoms improved. After 4 years, both hips were pain-free with no evidence of osteoarthritis progression. OI can result in insufficiency fractures due to bone fragility in adolescence and adulthood or later, and none of the cases of OI, except for the current case, were diagnosed as a result of bilateral SIF.

Background: Although certain genetic components have been reported as contributing factors for Perthes disease, its etiology remains unclear. We present a rare case of Perthes disease in a child with osteogenesis imperfecta (OI) caused by a mutation in the COL1A1 gene (NM_000088):exon25:c.1726C>T, (p.Gln576X). Case presentations: A 7-year-old boy was initially treated at our medical facility in March 2016 with a history of chronic pain in right hip joint and limping for a year. He was diagnosed as Perthes disease in the right hip joint. He underwent acetabular osteotomy and ipsilateral proximal femoral varus osteotomy for better containment. During the follow-ups, the right hip demonstrated a normal range of motion without pain, and the pelvic X-ray demonstrated Stulberg Type II hip joint with a round femoral head. In the latest admission in 2022, he suffered from a right femoral shaft fracture after petty violence. After reviewing his medical history, he was suspected of having OI. The whole exome sequencing demonstrated a gene mutation in COL1A1 (OMIM 166200) and confirmed the diagnosis of OI. Telescopic nailing was used to treat the femoral shaft fracture. After the nailing of the right femur, the appearance of the lower extremity seemed normal and symmetrical. Conclusion: This study revealed that there might be an association between OI and Perthes disease. Our case report enriches the phenotypes of osteogenesis imperfecta and provides insight into the pathogenesis of LCPD.

A clinical case of a patient with neonatal epilepsy at the age of 5 months, with impaired bone formation, early osteoporosis and frequent limb fractures is described. Panel sequencing confirmed by Sanger sequencing revealed two independent hereditary diseases - osteogenesis imperfect type 1, associated with a mutation in the COL1A1 gene (c.2010delT) and benign non-familial infantile seizures associated with a mutation in the PRRT2 gene (c.649dupC). A unique clinical case of a combination of these diseases is presented.
Описан клинический случай пациента с неонатальной эпилепсией в возрасте 5 мес жизни, с нарушением формирования костной ткани, ранним остеопорозом и частыми переломами конечностей. Методами панельного секвенирования и подтверждающего секвенирования по Сэнгеру выявлены две независимые наследственные болезни — несовершенный остеогенез 1-го типа, ассоциированный с мутацией в гене COL1A1 (с.2010delT), и доброкачественные несемейные инфантильные приступы, ассоциированные с мутацией в гене PRRT2 (c.649dupC). Представлен уникальный клинический случай сочетания данных заболеваний.

The demand for collagen has been increasing over years due to its wide application in food, cosmetics and biomedicine industries. The synthesis of collagen protein in fish depends on instructions provided by collagen, type I, alpha 1 (COL1A1) gene. However, cloning, tissue distribution and mRNA expression of COL1A1 gene in a gel-producing Chu\'s croaker (Nibea coibor) is currently unknown. This study cloned the cDNA of COL1A1 gene (GenBank accession number: MK641512) from six N. coibor fish. The distribution and mRNA expression pattern of COL1A1 was analyzed in eight tissues of N. coibor. The COL1A1 cDNA had a full length of 6130 bp and contained a 4344 bp open reading frame (ORF) encoding a polypeptide of 1448 amino acids. The homology of N. coibor COL1A1 amino acid had 98% similarity with Larimichthys crocea, indicating conservatism with other members in same family (Sciaenidae). The deduced polypeptide contained the same signal peptides, C-propeptide and N-propeptide domains, and triple helix domains, which are the characteristics of type I collagen in vertebrates. The mRNA of COL1A1 gene was expressed significantly higher in the spine of N. coibor than in all other tissues (P < 0.05), followed by swim bladder, skin and scales. The swim bladder had higher collagen and hydroxyproline contents than other tissues, followed by spine >, scales > and > skin (P < 0.05). Our study successfully cloned the COL1A1 gene from N. coibor for the first time. The COL1A1 gene contained all the features of collagen pro-α1(I) chain proteins, and shared high homology with other marine teleost. COL1A1 gene in N. coibor is highly expressed in spine and swim bladder, consistent with collagen distribution. Our study contributes to better understanding on collagen biosynthesis in N. coibor tissues for various industrial uses.

Osteogenesis imperfecta (OI) is a genetic disease with an estimated prevalence of 1 in 13,500 and 1 in 9700. The classification into subtypes of OI is important for prognosis and management. In this study, we established a clinical severity prediction model depending on multiple features of variants in COL1A1/2 genes.
BACKGROUND: Ninety percent of OI cases are caused by pathogenic variants in the COL1A1/COL1A2 gene. The Sillence classification describes four OI types with variable clinical features ranging from mild symptoms to lethal and progressively deforming symptoms.
METHODS: We established a prediction model of the clinical severity of OI based on the random forest model with a training set obtained from the Human Gene Mutation Database, including 790 records of the COL1A1/COL1A2 genes. The features used in the prediction model were respectively based on variant-type features only, and the optimized features.
RESULTS: With the training set, the prediction results showed that the area under the receiver operating characteristic curve (AUC) for predicting lethal to severe OI or mild/moderate OI was 0.767 and 0.902, respectively, when using variant-type features only and optimized features for COL1A1 defects, 0.545 and 0.731, respectively, for COL1A2 defects. For the 17 patients from our hospital, prediction accuracy for the patient with the COL1A1 and COL1A2 defects was 76.5% (95% CI: 50.1-93.2%) and 88.2% (95% CI: 63.6-98.5%), respectively.
CONCLUSIONS: We established an OI severity prediction model depending on multiple features of the specific variants in COL1A1/2 genes, with a prediction accuracy of 76-88%. This prediction algorithm is a promising alternative that could prove to be valuable in clinical practice.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and predisposition to fractures, bone deformities and other major signs such as dentinogenesis imperfecta, blue sclera and deafness. Over 90% of OI cases are caused by mutations in the COL1A1 and COL1A2 genes and the inheritance is autosomal dominant.
METHODS: We present a case of a couple requesting genetic counseling, because the man was diagnosed with OI on a clinical and radiological basis and the woman was pregnant. Whole exomes sequencing (WES) was performed in order to identify the mutation (s), followed by prenatal diagnosis.
RESULTS: WES identified a rare splicing mutation c.1155 + 1G > C in the COL1A1 gene recognized to be pathogenic and subsequently confirmed by next generation sequencing. The carrier state of the mutation was excluded for the fetus, so the pregnancy was further pursued and a healthy baby was born at term.
CONCLUSIONS: WES is a new and effective technique for detecting pathogenic variants in monogenic diseases and it is preferable to use such a technique in diseases with genetic heterogeneity especially when time does not allow another time-consuming diagnostic technique such classical Sanger sequencing. WES offers possibility to expand the global spectrum of OI pathogenic variants enabling the diagnosis of the disease.

Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone fragility and fractures, and associated with bone deformity, short stature, dentin, ligament and blue‑gray eye sclera. OI is caused by a heterozygous mutation in collagen α‑1(I) chain (COL1A1) or collagen α‑2(I) chain (COL1A2) genes that encode α chains of type I collagen. Collagen α chain peptide contains an N‑propeptide, which has a role in assembly and processing of collagen. Point mutations in the N‑propeptide domain appear to trigger OI. In the present study, a novel heterozygous missense mutation, c.281T>A (p.Val94Asp), was identified in the von Willebrand C domain of N‑terminal of type I collagen in an individual with type IV OI. The majority of N‑terminal mutations are associated with OI/Ehlers‑Danlos syndrome (EDS); however, in the present study, the affected individual did not suffer from EDS and the level of serum phosphorus of the patient was low (0.67 mmol/l). A number of clinical phenotypes were observed at the same variation site or in the same region on the polypeptide chain of COL1A, which suggests that additional genetic and environmental factors may influence the severity of OI. The present study may provide insight into the phenotype‑genotype association in collagen-associated diseases and improve clinical diagnosis of OI.

CONCLUSIONS: The two discovered mutations in COL1A1 gene, although first reported in China, are recurrent ones that have also been found elsewhere in type I osteogenesis imperfecta patients, suggesting their role in pathogenesis of Van der Hoeve syndrome.
OBJECTIVE: The aim of this study is to find mutational patterns of COL1A1 gene that may account for the putative Van der Hoeve syndrome in the patients carrying symptoms of osteogenesis imperfecta, blue sclera, and conductive deafness.
METHODS: Genomic DNA was extracted from the blood of each patient and exons of COL1A1 gene were amplified using PCR and sequenced.
RESULTS: Sequencing in some of the two family members revealed point mutations in exon 26 (c.1792C > T) and exon 43 (c.3076C > T) of COL1A1 gene, respectively.

OBJECTIVE: To analyze COL1A1/2 mutations in prenatal-onset OI for determine the proportion of mutations in type I collagen genes among prenatal onset OI and to provide additional data for genotype-phenotype analyses.
METHODS: Ten cases of severe fetal short-limb dwarfism detected by antenatal ultrasonography were referred to our center. Before the termination of pregnancy, cordocentesis was performed for fetal karyotype and COL1A1/2 gene sequencing analysis. Postmortem radiographic examination was performed at all instances for definitive diagnosis.
RESULTS: COL1A1 and COL1A2 SNP and mutations were identified in all the cases. Among these, one synonymous SNP and four synonymous SNPs were recognized in COL1A1/2, respectively, seven cases have distinct heterozygous mutations and six new COL1A1/2 gene mutations were identified.
CONCLUSIONS: There has been substantial progress in the identification of the molecular defects responsible for skeletal dysplasias. With the constant increase in the number of identified mutations in COL1A1 and COL1A2, genotype-phenotype correlation is becoming increasingly pertinent.

OBJECTIVE: The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study.
METHODS: A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method.
RESULTS: Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher\'s exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher\'s exact test).
CONCLUSIONS: The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.