A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss

Abstract Objectives: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. Methods: The basic clinical data of Ol proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. Results: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the Ol progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. Conclusion: The clinical symptoms of the Ol proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for Ol patients with hearing loss. Level of evidence: Level 4.

A novel mutation in COL1A1 causing osteogenesis imperfecta/hearing loss.

OBJECTIVES: To screen the COL1A1 and COL1A2 gene mutation sites in a family with type I osteogenesis imperfecta (OI)/hearing loss and analyze the characteristics and recovery of hearing loss in patients with osteogenesis imperfecta. METHODS: The basic clinical data of OI proband and her parents were collected, and the COL1A1 and COL1A2 genes were detected in peripheral blood by PCR amplification and generation Sanger sequencing. Literature of stapedial surgery in patients with osteogenesis imperfecta was collected. RESULTS: The heterozygous mutation of the 26 exon c.1922_1923 ins C in the OI progenitor COL1A1 gene led to the amino acid frameshift mutation of p.Pro 601FS, which was not detected in the phenotypic parents. The homozygous of exon 28 c.1782>G in COL1A2 was detected in the proband and her parents, resulting in changes in the protein p.Pro 549Ala. CONCLUSION: The clinical symptoms of the OI proband is caused by heterozygous mutation of the 26 exon c.1922_1923 ins C in COL1A1 gene. Stapedial surgery can provide short-term and long-term hearing benefits for OI patients with hearing loss. LEVEL OF EVIDENCE: Level 4.

Association of PRKAA1 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

ABSTRACT Objective: Studies have indicated that AMPK play critical roles in the regulation of innate immunity and inflammatory responses. However, the role of the polymorphisms of PRKAA1 gene in immune-response to infectious organisms remains unknown. To evaluate the potential role of PRKAA1/AMPKα1 in the immune-response to HBV, we conducted this case-control study. Methods: We recruited 276 patients (145 men and 131 women; average age, 51.6 years) with chronic HBV infection (CHB) and 303 healthy controls (166 men and 137 women; average age, 54.2 years). All the subjects were unrelated individuals of Chinese Han Population. Three SNPs of PRKAA1gene were tested. Results: Rs1002424 polymorphism showed significant difference in the allele frequencies, but no difference in the genotype frequencies (allele: p = 0.039411, OR95%CI = 0.783479 [0.621067-0.988362]; genotype: p = 0.104758); rs13361707 polymorphism showed significance in allele analysis, but not in genotype analysis (allele: p = 0.034749, OR95%CI = 1.284303 [1.017958-1.620335]; genotype: p = 0.098027); rs3792822 polymorphism was demonstrated to have significant differences in both genotype and allele frequencies between cases and controls (allele: p = 0.029286, OR95%CI= 0.741519 [0.566439-0.970716]; genotype: p = 0.034560). The haplotype results showed that CTG and TCA in the rs13361707-rs1002424-rs3792822 block were significantly associated with the happening of HBV (CTG: p = 0.036854, OR95%CI = 1.281 [1.015-1.617]; p = 0.030841, OR95%CI = 0.743 [0.568-0.973]). Conclusion: These findings suggest that PRKAA1 polymorphisms may contribute to the susceptibility of chronic HBV infection in Chinese Han origin.

Association of PRKAA1 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population.

OBJECTIVE: Studies have indicated that AMPK play critical roles in the regulation of innate immunity and inflammatory responses. However, the role of the polymorphisms of PRKAA1 gene in immune-response to infectious organisms remains unknown. To evaluate the potential role of PRKAA1/AMPKα1 in the immune-response to HBV, we conducted this case-control study. METHODS: We recruited 276 patients (145 men and 131 women; average age, 51.6 years) with chronic HBV infection (CHB) and 303 healthy controls (166 men and 137 women; average age, 54.2 years). All the subjects were unrelated individuals of Chinese Han Population. Three SNPs of PRKAA1gene were tested. RESULTS: Rs1002424 polymorphism showed significant difference in the allele frequencies, but no difference in the genotype frequencies (allele: p=0.039411, OR95%CI=0.783479 [0.621067-0.988362]; genotype: p=0.104758); rs13361707 polymorphism showed significance in allele analysis, but not in genotype analysis (allele: p=0.034749, OR95%CI=1.284303 [1.017958-1.620335]; genotype: p=0.098027); rs3792822 polymorphism was demonstrated to have significant differences in both genotype and allele frequencies between cases and controls (allele: p=0.029286, OR95%CI= 0.741519 [0.566439-0.970716]; genotype: p=0.034560). The haplotype results showed that CTG and TCA in the rs13361707-rs1002424-rs3792822 block were significantly associated with the happening of HBV (CTG: p=0.036854, OR95%CI=1.281 [1.015-1.617]; p=0.030841, OR95%CI=0.743 [0.568-0.973]). CONCLUSION: These findings suggest that PRKAA1 polymorphisms may contribute to the susceptibility of chronic HBV infection in Chinese Han origin.

Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma.

AIM: Matrix metalloproteinase (MMP)-14 and MMP-19 have been demonstrated to play an important role in the development of human gliomas. However, their prognostic values are not clear. The aim of this study was to investigate whether co-expression of MMP-14 and MMP-19 has prognostic relevance in human gliomas. METHODS: Immunohistochemistry and western blot were used to investigate the expression of MMP-14 and MMP-19 proteins in 128 patients with gliomas. RESULTS: The expression levels of MMP-14 and MMP-19 proteins in glioma tissues were both significantly higher (both P < 0.001) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis, which was confirmed by the western blot analysis. Additionally, the overexpression of either MMP-14 or MMP-19 was significantly associated with the advanced WHO grade (both P = 0.02), the low Karnofsky performance score (KPS) (P = 0.008 and 0.01, respectively) and the poor overall survival (both P = 0.01). Moreover, the Multivariate Cox proportional-hazards regression analysis revealed that the increased expressions of MMP-14 and MMP-19 were both independent prognostic factors for poor overall survival (both P = 0.02). Furthermore, the co-expression of MMP-14 and MMP-19 was additively and more significantly (P = 0.006) associated with adverse prognosis in patients with gliomas than respective expression of MMP-14 and MMP-19. CONCLUSIONS: These findings indicated for the first time that the co-expression of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.