Osteogenesis Imperfecta With Cerebral Atherosclerosis: A Family Report

Background: Osteogenesis imperfecta (OI) is a rare hereditary connective tissue disease. It is mainly associated with pathogenic variants in COL1A1 or COL1A2. Patients with OI usually have repeated history of bone fractures. Besides, osteogenesis imperfecta is associated with some cardiovascular complications, such as aortic and mitral valve dysfunction, aneurysm and aortic dissection. But the relationship between these diseases has not been well studied. Case Presentation: A 55-year-old man was admitted to our hospital mainly due to “dizziness for 2 hours”. He had a 4-month history of hypertension and a history of smoking for more than 20 years. He had no history of drinking alcohol. He had hunchback and O-type legs. Besides, the patient and some of his relatives had a history of repeated brittle fractures,which was considered as “osteogenesis imperfecta”. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. CT and MRI revealed multiple systemic arteriosclerosis, including vertebral artery, posterior inferior cerebellar artery, cervical artery, and bilateral cerebellar multiple lacunar cerebral infarction. The blood sample of the patient was tested by whole exome sequencing, and the saliva samples of the patient’s family members were tested by Sanger sequencing. A mutation c.3159 + 2T > A was detected in COL1A2 gene associated with OI, also found in the other affected family members, which had not been reported before. It was a segregating mutation in the family. The clinical severity of the family members was heterogeneous. Discussion: This case is worth learning from the following aspects: 1. A pathogenic heterozygous mutation, c.3159 + 2T > A was detected in COL1A2 gene in the patient with OI, which is not reported in previous cases of OI. 2. The clinical manifestation of OI in this family varies to a certain extent, from simple tooth disintegration to severe fracture deformity. The most serious patient of his family was unable to walk. It presented the clinical heterogeneity of OI. Further basic researh on the mutation site of related gene of OI are needed. 3. We found the possibility of developing cerebral atherosclerosis in patients with OI. Therefore, patients with OI should give up smooking, exercise properly and keep on a low fat diet. They should pay attention to control blood pressure and blood lipid so as to reduce the risk of atherosclerosis. Conclusion: A c.3159 + 2T>A mutation in COL1A2 gene detected by whole exome sequencing was the causing reason of OI, the discovery enriched the gene mutation spectrum of OI. We also found that OI may have relationship with premature atherosclerosis, and the abnormal bones of the cervical spine may lead to vertebrobasilar ischemia.

Single Nucleotide Polymorphisms in COL1A2 Gene and Dental Fluorosis Among 4 and 8-Year-Old Nigerian Children

Aim: To determine the association between single nucleotide polymorphisms (SNPs) within the COL1A2 gene and dental fluorosis among 4- and 8-year-old Nigerian children. Methods: A cross-sectional study was undertaken among 125 four and eight-year-old Nigerian children living in naturally fluoridated areas of Ibadan, Nigeria. Drinking and cooking water samples were collected for F analysis. Buccal mucosa swabs were collected from all children and genomic DNA extracted. Presence or absence of the SNP within the COL1A2 gene was identified by PCR and DNA sequencing for 70 of the participants. Results: The median (minimum, maximum) F concentration of drinking and cooking water were 0.05 (<0.1, 3.0) mg/L and 0.01 (<0.1, 4.0) mg/L respectively. The majority of the study participants (52.9%) were heterozygous for the SNP. There was a statistically significant association between F concentration in drinking water and the occurrence of dental fluorosis (p=0.04). F concentration in drinking water was the only statistically significant predictor of dental fluorosis (p=0.03, OR=3.64(CI=1.11-11.94)) after adjusting for F concentration in cooking water and SNPs. The risk of dental fluorosis tended to increase with the presence of SNPs AA and AC (RR > 1) but this association was not statistically significant. Conclusion: The majority of the study participants had the heterozygote SNP AC genotype of COL1A2 gene. F concentration in drinking water was the only statistically significant predictor of dental fluorosis. The risk of dental fluorosis tended to increase with the presence of SNPs AA and AC (RR > 1) but was not statistically significant.

Association between col1a2 Polymorphism and the Occurrence of Pelvic Organ Prolapse in Brazilian Women

Objective To evaluate the rs42524 polymorphism of the procollagen type I alpha (α) 2 (COL1A2) gene as a factor related to the development of pelvic organ prolapse (POP) in Brazilian women. Methods The present study involved 112 women with POP stages III and IV (case group) and 180 women with POP stages zero and I (control group). Other clinical data were obtained by interviewing the patients about their medical history, and blood was also collected from the volunteers for the extraction of genomic DNA. The promoter region of the COL1A2 gene containing the rs42524 polymorphism was amplified, and the discrimination between the G and C variants was performed by digestion of the polymerase chain reaction (PCR) products with the MspA1I enzyme followed by agarose gel electrophoresis analysis. Results A total of 292 women were analyzed. In the case group, 71 had the G/G genotype, 33 had the G/C genotype, and 7 had the C/C genotype. In turn, the ratio in the control group was 117 G/G, 51 G/C, and 11 C/C. There were no significant differences between the groups. Conclusion Our data did not show an association between the COL1A2 polymorphism and the occurrence of POP.