In this report, we investigated the frequency and spectrum of mitochondrial 12S rRNA variants in a large cohort of 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. Mutational analysis of 12S rRNA gene in these subjects identified 68 (54 known and 14 novel) variants. The frequencies of known 1555A>G and 1494C>T mutations were 3.96% and 0.18%, respectively, in this cohort with nonsyndromic and aminoglycoside-induced hearing loss. Prevalence of other putative deafness-associated mutation at positions 1095 and 961 were 0.61% and 1.7% in this cohort, respectively. Furthermore, the 745A>G, 792C>T, 801A>G, 839A>G, 856A>G, 1027A>G, 1192C>T, 1192C>A, 1310C>T, 1331A>G, 1374A>G and 1452T>C variants conferred increased sensitivity to ototoxic drugs or nonsyndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA. However, other variants appeared to be polymorphisms. Moreover, 65 Chinese subjects carrying the 1555A>G mutation exhibited bilateral and sensorineural hearing loss. A wide range of severity, age-of-onset and audiometric configuration was observed among these subjects. In particular, the sloping and flat shaped patterns were the common audiograms in individuals carrying the 1555A>G mutation. The phenotypic variability in subjects carrying these 12S rRNA mutations indicated the involvement of nuclear modifier genes, mitochondrial haplotypes, epigenetic and environmental factors in the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptMitochondrion. Author manuscript; available in PMC 2011 June 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript phenotypic manifestation of these mutations. Therefore, our data demonstrated that mitochondrial 12S rRNA is the hot spot for mutations associated with aminoglycoside ototoxicity.

No abstract

ObjectivesPrimary Sjogren's syndrome (pSS) is an important cause of pulmonary arterial hypertension (PAH), which remains insufficiently studied and needs attention. This study aimed to investigate the clinical characteristics, risk factors, prognosis and risk assessment of pSS-PAH.MethodsWe established a multicentre cohort of pSS-PAH diagnosed by right heart catheterisation (RHC). The case-control study was conducted with pSS-non PAH patients as a control group to identify the risk factors for PAH. In the cohort study, survival was calculated, and risk assessment was performed at both baseline and follow-up visits.ResultsIn total, 103 patients with pSS-PAH were enrolled, with 526 pSS-non PAH patients as controls. The presence of anti-SSB (p<0.001, OR=4.095) and anti-U1RNP antibodies (p<0.001, OR=29.518), the age of pSS onset (p<0.001, OR=0.651) and the positivity of corneal staining (p=0.003, OR=0.409) were identified as independent risk factors for PAH. The 1-, 3- and 5-year survival rates were 94.0%, 88.8% and 79.0%, respectively. Cardiac index (p=0.010, HR=0.161), pulmonary vascular resistance (p=0.016, HR=1.105) and Sjogren's syndrome disease damage index (SSDDI, p=0.006, HR=1.570) were identified as potential predictors of death in pSS-PAH. Long-term outcomes were improved in patients in the low-risk category at baseline (p=0.002) and follow-up (p<0.0001).ConclusionThe routine screening of PAH is suggested in pSS patients with early onset and positivity for anti-SSB or anti-U1RNP antibodies. Patients' prognosis might be improved by improving reserved cardiopulmonary function, by achieving a damage-free state and especially by achieving low-risk category, which supports the treat-to-target strategy for pSS-PAH.