Mutational and structural characteristics of four novel heterozygous C-propeptide mutations in the proα1(I) collagen gene in Chinese osteogenesis imperfecta patients.

OBJECTIVE: Osteogenesis imperfecta (OI) with C-propeptide mutations in proα1(I) collagen gene are rarely reported. We report four novel C-propeptide mutations in COL1A1 gene from Chinese OI patients. METHODS: Clinical characteristics and radiographic findings were described for four OI patients with C-propeptide mutations in proα1(I) collagen gene. Mutations were identified by traditional DNA sequencing based on PCR. The locations of mutations were mapped, and in silico prediction was conducted to analyse their effects on protein structure. Histology studies of skin, bone and muscle tissues were performed. RESULTS: All four C-propeptide heterozygous mutations identified were in the COL1A1 gene. Heterozygous mutation of c.4021C>T (p.Q1341X) disrupted the chain recognition sequences and was found in patients with type IV OI. Mutations of c.3893C>A (p.T1298N) and c.3897C>A (p.C1299X) impeded the formation of disulphide bonds and were associated with type IV OI phenotype. Missense mutation of c.3835A>C (p.N1279H) disrupted Ca(2+) binding and led to a severe type III OI phenotype. In silico programs predicted damaging effects for the patients with type III OI and the creation of an exonic splicing enhancer hexamer sequence for the type IV patients. Expansion of the bone marrow cavity and disorganization of osteocyte alignment was evident in bone specimens; and muscle atrophy and enlargement of intramuscular connective tissue were found in muscle specimens. CONCLUSIONS: Four novel C-propeptide mutations in proα1(I) collagen gene were identified in Chinese OI patients, and their clinical severity ranged from moderate type IV to severe type III. In silico prediction of the mutation effect and histological characteristics of tissue specimens was in accordance with the OI phenotypes.

Viral aetiology in adults with acute upper respiratory tract infection in Jinan, Northern China.

Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14-25-year-old group than in the 26-65-year-old group. Codetection rates were higher (7.52%) in the 14-25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.

Epidemiology of human respiratory viruses in children with acute respiratory tract infections in Jinan, China.

The viral etiologies of UTRIs and LTRIs in children in Jinan city were investigated between July 2009 and June 2010. Nasal and throat swabs were collected from 397 children with URTIs and bronchoalveolar lavage fluid specimens were collected from 323 children with LRTIs. RT-PCR/PCR was used to examine all samples for IFV, PIV, RSV, RV, hMPV, HBoV, CoV, ADV, RSV, and EV. Viral pathogens were detected in 47.10% of URTI samples and 66.57% samples, and the incidence of viral coinfection was 5.29% and 21.05%, respectively. IFV was the most common virus in URTIs, with a detection rate of 19.40%, followed by PIV (10.83%), RV (10.58%), and EV (6.30%). For LRTIs, PIV and RV were both detected in 27% of samples, followed by RSV (9.91%), HBoV (8.36%), IFV (5.57%), and hMPV (5.57%). RSV and HBoV were more prevalent in the youngest children of no more than six months. Meanwhile, RV, PIV, and RSV were the most frequent viruses combined with bacterial pathogens in LRTIs. In conclusion, the spectrum of respiratory virus infections in URTIs and LRTIs differed in terms of the most common pathogens, seasonal distribution, and coinfection rate.