ABSTRACT
Lysosomes contribute to cellular homeostasis via processes including macromolecule degradation, nutrient sensing, and autophagy. Defective proteins related to lysosomal macromolecule catabolism are known to cause a range of lysosomal storage diseases; however, it is unclear whether mutations in proteins involved in homeostatic nutrient sensing mechanisms cause syndromic sensory disease. Here, we show that SLC7A14, a transporter protein mediating lysosomal uptake of cationic amino acids, is evolutionarily conserved in vertebrate mechanosensory hair cells and highly expressed in lysosomes of mammalian cochlear inner hair cells (IHCs) and retinal photoreceptors. Autosomal recessive mutation of SLC7A14 caused loss of IHCs and photoreceptors, leading to presynaptic auditory neuropathy and retinitis pigmentosa in mice and humans. Loss-of-function mutation altered protein trafficking and increased basal autophagy, leading to progressive cell degeneration. This study implicates autophagy-lysosomal dysfunction in syndromic hearing and vision loss in mice and humans.
Subject(s)
Amino Acid Transport System y+ , Hearing Loss, Central , Lysosomes , Retinitis Pigmentosa , Amino Acid Transport System y+/genetics , Animals , Hearing Loss, Central/metabolism , Humans , Lysosomes/metabolism , Lysosomes/pathology , Mammals , Mice , Mutation , Retinitis Pigmentosa/genetics , Retinitis Pigmentosa/metabolismABSTRACT
OBJECTIVE: To expound the roles of mTOR and NF-kB signaling pathway in intermittent hypoxia (IH)-induced damage of hippocampal neurons. METHODS: For rat experiments, mTOR inhibitor (Rapamycin, Rapa) and NF-κB signaling inhibitor (ammonium pyrrolidine dithiocarbamate, PDTC) were applied to inhibit mTOR and NF-κB signaling, respectively. For neuron experiments, hippocampal neurons from rat were successfully cultured. Different concentrations of Rapa and PDTC were added to the cultured hippocampal neurons. Rat or primary hippocampal neurons were exposed to normoxic or IH conditions after administration of Rapa and PDTC. The effects of Rapa and PDTC administration on learning and memory ability of rats and hippocampal injury after IH exposure were assayed by Morris water maze and H&E staining. Electron microscope was utilized to examine primary hippocampal neuron ultrastructure changes after IH exposure and Rapa or PDTC administration. The expressions of NF-κB-p65, IκBα, IKKß, BDNF, TNF-α, IL-1ß, PSD-95 and SYN in hippocampal neurons were examined. RESULTS: Compared with normal control rats or neurons, IH-treated group had elevated expression levels of NF-kB, TNF-α and IL-1ß and suppressed expression level of BDNF, PSD-95 and SYN. These results were reversed upon pre-treatment with Rapa and PDTC. Furthermore, IκBα and IKKß expressions were down-regulated in IH group. No notable difference was manifested in PDTC pre-treatment group, while a prominent increase was shown after Rapa pre-administration. CONCLUSION: The administration of PDTC and Rapa could prevent IH-induced hippocampal neuron impairment, indicating that inhibition of the mTOR and NF-κB pathway may likely act as a therapeutic target for obstructive sleep apnea.
Subject(s)
Antioxidants/pharmacology , Hippocampus/metabolism , Hypoxia/metabolism , NF-kappa B/metabolism , Neurons/metabolism , Protein Kinase Inhibitors/pharmacology , Pyrrolidines/pharmacology , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism , Thiocarbamates/pharmacology , Animals , Cells, Cultured , Disease Models, Animal , Hippocampus/drug effects , Hypoxia/drug therapy , Male , NF-kappa B/antagonists & inhibitors , Neurons/drug effects , Rats , Rats, Wistar , Signal Transduction/drug effects , Signal Transduction/physiology , Sleep Apnea, Obstructive/drug therapy , Sleep Apnea, Obstructive/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitorsABSTRACT
INTRODUCTION: Occupational stress is considered to be a harmful physical and emotional response to an individual's psychological and/or physiological state in the work environment and is highly prevalent among medical staff. However, few epidemiological studies have investigated occupational stress in medical staff. Our study aims to explore the characteristics of occupational stress and its relationship with dyslipidemia in Chinese medical staff at tertiary hospitals and establish the basis for future preventive strategies. METHODS: A cross-sectional study was conducted in three tertiary public hospitals in Wenzhou City, Zhejiang Province, China. Data were collected using random sampling procedures to examine demographic characteristics and job-related data. The participants completed the Occupational Stress Inventory-Revised (OSI-R) questionnaires and serum lipids tests. Partial correlation analysis was conducted to explore the relationship between occupational stress and dyslipidemia. RESULTS: A total of 1,176 medical staff responses to questionnaires were obtained. The occupational stress levels of medical staff were higher than those of normative populations, while their coping resources were lower. Most of the subscales of occupational stress demonstrated higher results for doctors and males than for nurses and females with crude analyses. Each subscale of OSI-R was found to be associated with a different type of blood lipid level. CONCLUSIONS: The occupational stress level of medical staff in tertiary public hospitals in Wenzhou was high, and occupational stress may contribute to dyslipidemia. An investigation into occupational stress levels and their association with dyslipidemia in this population could draw more attention to medical staff in tertiary public hospitals.
Subject(s)
Dyslipidemias , Occupational Stress , China/epidemiology , Cross-Sectional Studies , Dyslipidemias/epidemiology , Female , Hospitals, Public , Humans , Male , Medical Staff , Occupational Stress/epidemiology , Stress, Psychological/epidemiology , Surveys and Questionnaires , Tertiary Care CentersABSTRACT
Objectives: The objective of this study was to estimate the prevalence of dyslipidemia and associated influencing factors in young adults in the southeastern coastal area of China. Methods: This study adopted a cross-sectional survey and included 7,859 young people who underwent examinations at three hospitals in Wenzhou, Zhejiang Province, China. All subjects completed a questionnaire in the form of face-to-face interviews and underwent anthropometric measurements and biochemical tests. The continuous data are presented as the means ± standard deviations and were compared using Student's t-tests. The categorical variables are presented as proportions. The influencing factors associated with dyslipidemia were evaluated through a multivariate logistic regression. Results: The prevalence of dyslipidemia among young adults aged 18-45 years in the southeastern coast of China was high with 7.1, 15.0, 22.9, and 4.0% for high-total cholesterol (TC), high-triglyceride (TG), low-high-density lipoprotein cholesterol (HDL-C), and high-low-density lipoprotein cholesterol (LDL-C). Among those with dyslipidemia, a statistically significant difference in sex was observed, and all types of dyslipidemia were associated with smoking and alcohol consumption. However, those with high-TG, high-LDL, and low-HDL levels did not significantly differ in education level or occupation. The presence of dyslipidemia was significantly associated with increased age, the male sex (OR: 1.85, 95% CI: 1.39-2.21), smoking (OR: 2.02, 95% CI: 1.98-2.13), alcohol consumption (OR: 1.33, 95% CI: 1.16-1.63), overweight or obesity (OR: 2.01, 95% CI: 1.79-2.41), and intellectual work (OR: 1.36, 95% CI: 1.11-1.72). Conclusion: The prevalence of dyslipidemia among young adults aged 18-45 years in the southeastern coast of China was high. To prevent dyslipidemia at an early age, it is essential to conduct effective intervention programs targeting risk factors and to implement routine screening programs.
Subject(s)
Dyslipidemias , Adolescent , Adult , Alcohol Drinking/epidemiology , China/epidemiology , Cross-Sectional Studies , Dyslipidemias/epidemiology , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Obesity/epidemiology , Overweight/epidemiology , Prevalence , Smoking/epidemiology , Triglycerides/blood , Young AdultABSTRACT
OBJECTIVES: To assess the safety and immunogenicity of a nonadjuvant human papillomavirus (HPV) type 6 L1 virus-like particle (VLP) vaccine in recurrent respiratory papillomatosis (RRP) in local Chinese patients. METHODS: Patients with RRP who had undergone surgical treatment before intramuscular administration of an escalating dose of HPV type 6 L1 VLPs (1, 5, and 25 µg at 4 weekly intervals) as part of their treatment were followed up for more than 10 years. Efficacy was assessed by detecting the vaccine-induced type-specific antibody titer, calculating the intersurgical interval, and observing recurrence or remission of papillomas after receiving the vaccine. RESULTS: Nonadjuvant HPV vaccine was generally well tolerated, with no serious vaccine-related adverse episodes. It induced seroconversion for each vaccine-related HPV type. At week 12 (4 weeks after injecting 25 µg), the vaccine-induced type-specific antibody titer was significantly high. Analysis of all patients found a significant increase in the intersurgical interval and decrease in the scores. One patient (16.7%; female) experienced complete remission. Five patients (83.3%) (two males and three females) experienced partial remission. In total, complete or partial remission was achieved in six (100%) patients. CONCLUSIONS: Administration of nonadjuvant HPV type 6 L1 VLPs vaccine to RRP was generally well tolerated and highly immunogenic.
Subject(s)
Antibodies, Viral/blood , Capsid Proteins/administration & dosage , Human papillomavirus 6/immunology , Immunogenicity, Vaccine , Papillomavirus Infections/therapy , Papillomavirus Vaccines/administration & dosage , Respiratory Tract Infections/therapy , Vaccines, Virus-Like Particle/administration & dosage , Adolescent , Biomarkers/blood , Capsid Proteins/adverse effects , Capsid Proteins/immunology , Child , China , Clinical Trials, Phase I as Topic , Female , Humans , Male , Papillomavirus Infections/diagnosis , Papillomavirus Infections/immunology , Papillomavirus Infections/virology , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/immunology , Remission Induction , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/immunology , Respiratory Tract Infections/virology , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vaccines, Virus-Like Particle/adverse effects , Vaccines, Virus-Like Particle/immunologyABSTRACT
We did a clinical trial to determine whether olfactory mucosa lamina propria (OLP) transplants promote regeneration and functional recovery in chronic human spinal cord injury (SCI). The trial randomized 12 subjects to OLP transplants (n = 8) or control sham surgery (n = 4). The subjects received magnetic resonance imaging (MRI), electromyography (EMG), urodynamic study (UDS), American Spinal Injury Association impairment scale (AIS), and other functional assessments. OLP-transplanted subjects recovered more motor, sensory, and bladder function compared to sham-operated subjects. At 3 years after OLP transplant, one patient improved from AIS A to C and another recovered from AIS A to B, two recovered more than three segmental sensory levels, two had less spasticity, two had altered H-reflexes and SSEP, two regained bladder and anorectal sensation and had improved bladder compliance on UDS. OLP-treated patients had partial or complete tissue bridges at the injury site compared to cavitary gaps in sham-operated patients. The limited recovery suggests that OLP transplants alone do not have significant benefits but may provide a rationale for larger randomized trials or combination therapies.
Subject(s)
Olfactory Mucosa/transplantation , Spinal Cord Injuries/physiopathology , Spinal Cord Injuries/therapy , Adult , Chronic Disease , Demography , Double-Blind Method , Electromyography , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Middle Aged , Postoperative Care , Preoperative Care , Prospective Studies , Spinal Cord Injuries/surgery , Transplantation, Autologous/adverse effects , Treatment Outcome , Urodynamics , Young AdultABSTRACT
To evaluate the correlation between genetic mutations and the age in nonsyndromic hearing impairment (NSHI) and the clinical characteristics of NSHI, 215 patients with NSHI were enrolled between April 2006 and April 2012. All patients were divided into four groups according to ages of hearing loss onset and clinic presentation (0-3, 3-6, 6-18 and 18+ years). The mutations of GJB2 and mitochondria DNA (mtDNA) 1555G/C1494T were screened from peripheral blood samples in each age group. The prevalence of mutations and the age ratio were obtained. The study showed that 18.14% of all patients were found to have GJB2 mutations and 11.16% were found to have mtDNA A1555G/C1494T mutations. The prevalence of GJB2 mutation in adult group (5.26%) was lower than juvenile group who sought medical attention at 0-18 years of age (22.36%), while the prevalence of mtDNA A1555G/C1494T in adult group (31.48%) was higher than juvenile group (4.97%). Significant differences in the prevalence of GJB2 (χ2=7.108, P=0.008) and mtDNA A1555G/C1494T (χ2=20.852, P=0.000) were observed in both of two groups. The prevalence of GJB2 mutations between adult and juvenile groups according to ages of hearing loss onset was statistically significant different (0%, 20.10%, respectively, and P=0.023), while the prevalence of mtDNA A1555G/C1494T mutations was not different (14.29%, 11.34%, respectively, and P=0.698). The onset age of 66.67% of patients with GJB2 mutations was less than 1 year old, while the onset of patients with mtDNA A1555G/C1494T mutations could be found at any age group. Different standardizations of hearing loss could also show different results. These data strongly suggest that most of GJB2 mutations are found in congenital deafness and mtDNA A1555G/C1494T mutations mainly represent acquired deafness, which can be induced or aggravated by aminoglycoside antibiotics in all age groups and should be tested mainly ranging from 4 kHz to 8 kHz. Both newborn hearing screening and genetic testing are important to find early deafness.
Subject(s)
Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Mutation , Adolescent , Adult , Age Factors , Child , Child, Preschool , Connexin 26 , Connexins/genetics , DNA, Mitochondrial/genetics , Female , Genetic Testing , Humans , Infant , Male , Middle Aged , Mutation Rate , Young AdultABSTRACT
Mitochondrial 12S rRNA A1555AG mutation is one of the important causes of aminoglycoside-induced and nonsyndromic deafness. We report here the clinical, genetic and molecular characterization of 25 Chinese families carrying the A1555G mutation.Clinical and genetic characterizations of these Chinese families exhibited a wide range of penetrance, severity and age-at-onset of hearing impairment. The average penetrances of deafness were 28.1% and 21.5%, respectively, when aminoglycoside-induced hearing loss was included or excluded. Furthermore, the average age-of-onset for deafness without aminoglycoside exposure ranged from 1 and 15 years old. Their mitochondrial genomes exhibited distinct sets of polymorphisms including 16 novel variants, belonging to ten Eastern Asian haplogroups A, B, D, F, G, M, N and R, respectively. Strikingly, these Chinese families carrying mitochondrial haplogroup B exhibited higher penetrance and expressivity of hearing loss. In addition, 7 known secondary mutations and 21 variants resided at the highly conservative residues may enhance the penetrace of hearing loss in these Chinese families. Moreover, the absence of mutation in GJB2 gene suggested that GJB2 may not be a modifier for the phenotypic expression of the A1555G mutation in these Chinese families. These observations suggested that mitochondrial haplotypes and other modifiers may modulate the variable penetrance and expressivity of deafness among these Chinese families.
Subject(s)
Asian People/genetics , Hearing Loss/genetics , Mutation, Missense , RNA, Ribosomal/genetics , Amino Acid Sequence , Asian People/ethnology , Base Sequence , Child , Child, Preschool , China/ethnology , Connexin 26 , Connexins , DNA, Mitochondrial/chemistry , DNA, Mitochondrial/genetics , Female , Hearing Loss/ethnology , Humans , Infant , Male , Molecular Sequence Data , Nucleic Acid Conformation , Pedigree , RNA, Ribosomal/chemistryABSTRACT
OBJECTIVE: To assess the possible genotype-phenotype correlation for GJB2. METHODS: Retrospectively analyzed GJB2 gene mutations with non-syndromic hearing impairment (NSHI) patients and their families audiological data. Individuals were grouped, according to non-truncated mutant (non-truncating, NT) and truncating mutations (truncating, T), into T/T group, T/NT group and NT/NT group. And according to whether they carry 235delC, grouped into 235delC/235delC group, 235delC/Non-235del group and Non-235delC/Non-235delC group. RESULTS: Grouped according to whether the truncation mutants:Fisher exact statistical analysis showed that the degree of hearing loss among the three groups did not meet the random distribution (P = 0.003) , T/T group was significantly higher than T/NT group (P = 0.000) and NT/NT group (P = 0.000) on the degree of hearing loss. Grouped according to whether they carry 235delC mutation: degrees of hearing loss among the three groups were statistically significant differences. Respectively pairwise comparisons (Fisher exact test) found 235delC/235delC group was significantly higher than 235delC/Non-235delC on the degree of hearing loss group (P = 0.001) and Non-235delC/Non-235delC group (P = 0.000), 235delC/Non-235delC group higher than Non-235delC/Non-235delC group (P = 0.033). In GJB2 mutations homozygous and compound heterozygous mutation genotype:G109A/G109A, 235delC/512insAACG, 299delAT/G109A and 235delC/G109A degree of hearing loss caused by genotype was significantly lower than 235delC/235delC group. CONCLUSIONS: 235delC homozygotes have significantly more hearing impairment, when compared with 235delC/non-235delC compound heterozygotes. People with two non-235delC mutations have even less hearing impairment. Patients with non-truncation mutants (G109A) suffer from lighter hearing loss than truncation mutations(235delC, 299delAT).
Subject(s)
Connexins/genetics , Mutation , Adolescent , Adult , Aged , Aged, 80 and over , Child , Connexin 26 , Deafness/genetics , Genotype , Heterozygote , Humans , Infant , Infant, Newborn , Middle Aged , Pedigree , Young AdultSubject(s)
Bleomycin/therapeutic use , Hemangioma/drug therapy , Laryngeal Neoplasms/drug therapy , Pharyngeal Neoplasms/drug therapy , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
OBJECTIVE: To investigate the safety of peri-operative management on children with juvenile recurrent respiratory papilloma (JORRP). METHODS: A retrospective analysis was conducted on preoperative assessment, anesthesia methods and options, operative procedure, and postoperative airway maintenance in 28 JORRP children aged from ten months to seven years old. A total of 148 times of surgery was performed on these 28 children. RESULTS: One hundred and nine JORRP children graded one and two-degree dyspnea underwent surgery within 24 hours and were intubated successfully in the first attempt after intravenous induction. Thirty-nine emergency operations were performed in the children graded three and four-degree dyspnea, 35 of them were intubated successfully in the first attempt after inhalation induction and 4 succeeded in the second attempt. No complications occurred in 129 JORRP children postoperatively, 17 children suffered from mild dyspnea and relieved after oxygen inhalation, 2 children were intubated and sent to intensive care unit because of postoperative hypoxemia. All JORRP children got through the peri-operative period safely. The quality of pronunciation in 101 children improved markedly and 35 suffered from slight hoarseness on the 1st postoperative day. Three children had the tracheal tube of tracheostomy removed after receiving five, four and three operations respectively. Nineteen children were followed up for 2 - 5 years. Among them, one child did not relapse 3 years after surgical management.One child suffered from laryngostenosis postoperatively. No death occurred. CONCLUSION: Complete preoperative preparation, rational anesthesia methods, careful operative procedure and airway maintenance after surgery could increase the safety for children with recurrent respiratory papilloma.
Subject(s)
Laryngeal Neoplasms/surgery , Papillomavirus Infections/surgery , Perioperative Care , Respiratory Tract Infections/surgery , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
OBJECTIVE: To evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations, haplotypes, GJB2 gene mutations on phenotype of 1494C>T mutation, and to study the molecular pathogenic mechanism of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss. METHODS: Two Chinese Han pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic hearing loss were collected. The two probands and their family members underwent clinical, genetic and molecular evaluations including audiological examinations and mutational analysis of mitochondrial genome and GJB2 gene. RESULTS: Clinical evaluation revealed wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in both families, for which the penetrance of hearing loss was respectively 42.9% and 28.6% when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss were 14.3% and 14.3%. Sequence analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation, in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroups C4a1a and B4b1c, respectively. CONCLUSION: Mitochondrial 12S rRNA 1494C>T mutation probably underlie the deafness in both families. Lack of significant mutation in the GJB2 gene ruled out involvement of GJB2 in the phenotypic expression. However, aminoglycosides and other nuclear modifier genes may still modify the phenotype of the 1494C>T mutation in these families. The B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic hearing loss family carrying the 1494C>T mutation. The 1494C>T mutation seems to have occurred sporadically through evolution.
Subject(s)
DNA, Mitochondrial/genetics , Hearing Loss/chemically induced , Hearing Loss/genetics , Mutation , RNA, Ribosomal/genetics , Adult , Aminoglycosides/adverse effects , Asian People/genetics , Base Sequence , Connexin 26 , Connexins/genetics , Genetic Predisposition to Disease , Haplotypes , Humans , Male , Molecular Sequence Data , Pedigree , Phenotype , Young AdultABSTRACT
Mitochondrial DNA (mtDNA) mutations are one of the important causes of deafness. In particular, the 12S rRNA gene is the hot spots for mutations associated with both aminoglycoside ototoxicity and nonsyndromic deafness. In this report, a total of 318 Chinese pediatric hearing-impaired subjects were recruited from otology clinics in the Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of 12S rRNA gene. Mutational analysis identified 34 variants in the 12S rRNA gene in this cohort. The incidences of the known deafness-associated 1555A>G, 1494C>T and 1095T>C mutations were 9.1%, 0.6% and 1.25% in this cohort, respectively. Other mtDNA variants were evaluated by structural and phylogenetic analysis. Of these, the 839A>G and 1452T>C variants could confer increased sensitivity to aminoglycosides or nonsyndromic deafness as they were not present in 449 Chinese controls and localized at highly conserved nucleotides of the 12S rRNA. However, other variants appeared to be polymorphisms. These data further support the idea that mitochondrial 12S rRNA is one of major targets for aminoglycoside ototoxicity. These data have been providing valuable information to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.
Subject(s)
DNA, Mitochondrial/genetics , Hearing Loss/genetics , Mitochondria/genetics , RNA, Ribosomal/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Aminoglycosides/genetics , Asian People/genetics , Child , Child, Preschool , Cohort Studies , Female , Genetic Variation , Humans , Infant , Male , Middle Aged , Young AdultABSTRACT
OBJECTIVE: To investigate mutational spectrum and frequency of the mitochondrial 12S rRNA gene in Chinese subjects with aminoglycoside-induced and non-syndromic hearing loss. METHODS: Total of 456 subjects with non-syndromic hearing loss were recruited from seven schools for deaf-mutes in Zhejiang province. Genomic DNA was extracted from the whole blood, and then the DNA fragment was amplified spanning the 12S rRNA gene, followed by sequencing and analyzed. RESULTS: Thirty-one variants were identified by mutation analysis of 12S rRNA gene in these subjects. The frequency of the known 1555A > G mutation was 4.4% (20/456). Prevalence of other putative deafness-associated mutation at positions 961 and 1095 were 2.0% (9/456) and 0.7% (3/456) respectively. Furthermore, the 1027A > G, 1109T > C and 1431G > A variants conferred increased sensitivity to ototoxic drugs or non-syndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this 12S rRNA gene. Moreover, clinical data showed a wide range of age-of-onset, variety of severity and various audiometric configurations in subjects carrying the 1555A > G mutation. CONCLUSIONS: Our data demonstrated that the mitochondrial 12S rRNA gene is the hot spot for mutations associated with aminoglycoside ototoxicity and non-syndromic hearing loss. Nuclear modifier genes, mitochondrial haplotypes and environmental factors might play a role in the phenotypic manifestation of these mutations.
Subject(s)
DNA, Mitochondrial/genetics , Deafness/genetics , RNA, Ribosomal/genetics , Adolescent , Aminoglycosides/genetics , Asian People/genetics , Base Sequence , Child , DNA Mutational Analysis , Female , Humans , Male , Mutation , Nucleic Acid Conformation , Pedigree , Young AdultABSTRACT
OBJECTIVE: To study the effect of the mitochondrial 12S rRNA mutations on aminoglycoside-induced and nonsyndromic hearing loss, to carry out the clinical and molecular characterization of five Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss. METHODS: Five pedigrees of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss were collected, genomic DNA was extracted, and complete mitochondrial genomes and the gap junction protein beta 2 (GJB2) gene were amplified and sequenced. RESULTS: Clinical evaluation revealed a wide range of severity, age-at-onset and audiometric configuration of hearing impairment in the matrilineal relatives in these families. The penetrance rates of hearing loss in these pedigrees were 17.6%, 50.0%, 66.7%, 31.3% and 23.1%, with an average of 37.7%, when aminoglycoside-induced deafness was included. Sequence analysis of the complete mitochondrial genomes in these pedigrees identified the known 1555A>G mutation and distinct sets of mitochondrial DNA(mtDNA) polymorphisms belonging to Eastern Asian haplogroups D4b2b, B4c1b1, F3, C1 and D5a, respectively. Of these variants, ND1 L89T and CO3 A200T mutations resided at the highly conservative regions. However, there were no functionally significant mutations in tRNAs and rRNAs or secondary known mutations. No hearing loss related GJB2 gene mutation was observed. CONCLUSION: The lack of significant mutation in the ruled out the possible involvement of GJB2 in the phenotypic expression of the 1555A>G mutation in those affected subjects. However, aminoglycosides, mtDNA variations and other nuclear modifier genes may play an important role in the phenotypic manifestation of the 1555A>G mutation in these Chinese families.
Subject(s)
Aminoglycosides/adverse effects , Asian People/genetics , Ethnicity/genetics , Hearing Loss, Sensorineural/chemically induced , Hearing Loss, Sensorineural/genetics , Inheritance Patterns/genetics , Mothers , Adult , Amino Acid Sequence , Animals , Child , Child, Preschool , China/ethnology , Connexin 26 , Connexins/chemistry , Connexins/genetics , DNA Mutational Analysis , Female , Humans , Male , Molecular Sequence Data , Pedigree , Young AdultABSTRACT
GJB2, SLC26A4 (PDS) and mitochondrial DNA (mtDNA) have been associated with sensorineural hearing loss. In the present study, the clinical, genetic and molecular analysis of 14 cochlear implant recipients and their parents was studied from April 2006 to September 2007. Of the 14 subjects, 35.7% had gene mutations; 28.6% had homozygous GJB2 235delC mutation, whose parents carried heterozygous GJB2 235delC mutation; and 7.1% had mtDNA A1555G mutation, whose mother carried mtDNA A1555G mutation too. There was no SLC26A4 (PDS) mutation. These results strongly suggested that the mutation in GJB2 gene was a major cause of deafness in cochlear implant recipients and the mutation of mtDNA A1555G was another important cause. Genetic test of hot-spots and analysis of family constellation can offer an accurate genetic counseling to deaf family and reduce the incidence of hearing loss.
Subject(s)
Cochlear Implants , Hearing Loss/genetics , Pedigree , Adolescent , Child , Child, Preschool , Connexin 26 , Connexins , DNA Mutational Analysis , DNA, Mitochondrial/genetics , Female , Genetic Predisposition to Disease , Humans , Infant , MaleABSTRACT
OBJECTIVE: To study the relationship between human papilloma virus 11b virus like particles (HPV11bVLPS) serum antibody and the development and prognosis of juvenile larynx papilloma (JLP). METHODS: Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HPV11bVLP antibody (Ab) of 46 JLP's samples in different stage and 20 controls using HPV11bVLPS which was produced by recombinant bacilovirus in insect cells. Grouping: A: control group (n = 20); B: the time of onset was 1 years (n = 15); C: the time of onset was 2 years (n = 15); the patients were followed-up 1 year without recurrence (n = 8); E: The patients were followed-up 2 years without recurrence (n = 8). RESULTS: A value of HPV11bVLP Ab among A, B, C, D, E. group were: (0.073 +/- 0.035); (0.120 +/- 0.049); (0.137 +/- 0.057); (0.518 +/- 0.122); (0.557 +/- 0.144). There was a significant difference between JLP patients and the control group (P < 0.05). The level of HPV11bVLP Ab in (D + E) group (0.534 +/- 0.132) was higher than (B + C) group (0.128 +/- 0.053) (t = 14.90, P < 0.001). CONCLUSION: The results suggested that HPV serum antibody was produced in JLP with HPV infection. There is close relationship between the development and prognosis of the disease and the level of HPV11Ab in serum. The assay of serum HPV11bVLPAb and HPV-VLP could be used as immunological study of HPV11-infection associated disease.