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.

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea

Abstract Introduction: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. Objective: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. Methods: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. Results: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1β, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. Conclusion: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea.

INTRODUCTION: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. OBJECTIVE: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. METHODS: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. RESULTS: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1ß, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. CONCLUSION: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.