The purpose of this study was to compare the genotype/phenotype relationship between siblings with identical USH2A pathologic mutations and the consequent audiologic phenotypes, in particular degree of hearing loss (HL). Decade audiograms were also compared among two groups of affected subjects with different mutations of USH2A.
DNA samples from patients with Usher syndrome type II were analysed. The audiological features of patients and affected siblings with USH2A mutations were also examined to identify genotype-phenotype correlations.
Genetic and audiometric examinations were performed in 18 subjects from nine families with Usher syndrome type IIA.
Three different USH2A mutations were identified in the affected subjects. Both similarities and differences of the auditory phenotype were seen in families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found the group of affected subjects with different pathological mutations.
Our results indicate that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables, such as modifying genes, epigenetics or environmental factors which may be of importance for better understanding the etiology of Usher syndrome.
Investigate genetic causes of HI among the Inuit populations in the Arctic with a high prevalence of hearing impairment (HI).
A cross-sectional survey with population-based controls.
Forty-five patients, with sensorineural or mixed HI and an available blood sample for GJB2 sequencing from DNA, were selected from 166 east Greenlanders by specialist audiology examination, including pure-tone air and bone conduction audiometry from 125 Hz to 8000 Hz. Controls were 108 east- and 109 west-Greenlanders.
Forty-five patients with HI were included, 24 males and 21 females. Median age was 35 years (range: 5-76). The c.35delG allele frequency was 3.3%. One patient, homozygous for the c.35delG GJB2 mutation, had bilateral congenital profound HI. Another with mixed HI was heterozygous for the same mutation. Three were heterozygous for the p.V27I variant and one was heterozygous for the p.V153I variant. The frequency of the c.35delG mutation in the controls varied between 0.5% in west Greenland to 2.3% in east Greenland.
The c.35delG GJB2 mutation occurs in Greenland with low frequency. We conclude the main causes behind the prevalence of HI in this population are chronic otitis media, noise traumas, and/or unidentified genetic causes.
The purpose of the present study was to examine, first, whether hearing acuity predicts falls and whether the potential association is explained by postural balance and, second, to examine whether shared genetic or environmental effects underlie these associations.
Hearing was measured using a clinical audiometer as a part of the Finnish Twin Study on Aging in 103 monozygotic and 114 dizygotic female twin pairs aged 63-76 years. Postural balance was indicated as a center of pressure (COP) movement in semi-tandem stance, and participants filled in a fall-calendar daily for an average of 345 days after the baseline.
Mean hearing acuity (better ear hearing threshold level at 0.5-4 kHz) was 21 dB (standard deviation [SD] 12). Means of the COP velocity moment for the best to the poorest hearing quartiles increased linearly from 40.7 mm(2)/s (SD 24.4) to 52.8 mm(2)/s (SD 32.0) (p value for the trend = .003). Altogether 199 participants reported 437 falls. Age-adjusted incidence rate ratios (IRRs) for falls, with the best hearing quartile as a reference, were 1.2 (95% confidence interval [CI] = 0.4-3.8) in the second, 4.1 (95% CI = 1.1-15.6) in the third, and 3.4 (95% CI = 1.0-11.4) in the poorest hearing quartiles. Adjustment for COP velocity moment decreased IRRs markedly. Twin analyses showed that the association between hearing acuity and postural balance was not explained by genetic factors in common for these traits.
People with poor hearing acuity have a higher risk for falls, which is partially explained by their poorer postural control. Auditory information about environment may be important for safe mobility.
Cites: Am J Otolaryngol. 1999 Nov-Dec;20(6):371-810609481
Cites: J Gerontol A Biol Sci Med Sci. 2008 Feb;63(2):171-818314453
Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland; Department of Neurology, Oulu University Hospital, P.O. Box 20, FI-90029 Oulu, Finland. Electronic address: email@example.com.
Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes.
This study examined differences between a group of normal-hearing Caucasian and Chinese young adults on six tympanometric parameters. The goal of this study was to determine if the Chinese group had different low and multifrequency tympanometry results than the Caucasian group.
There were a total of 159 subjects (303 ears) between the ages of 18 and 34 years, with 76 subjects in the Caucasian group and 83 subjects in the Chinese group. Tympanometric data were gathered on a clinical immittance machine, the Virtual 310 equipped with a high frequency option. Four of the parameters-static admittance (SA), tympanometric width (TW), tympanometric peak pressure (TPP), and ear-canal volume (ECV)-were measured automatically at a standard 226 Hz frequency. The remaining two parameters-resonant frequency (RF) and SA up to 1,200 Hz-were measured by multifrequency, multicomponent tympanometry, using a mathematical approach.
The Chinese group had significantly lower SA, wider TW, more positive TPP, and lower ECV than their Caucasian counterparts. The parameter of SA up to 1,200 Hz showed a significant group effect (Caucasian versus Chinese) until 900 Hz in the male group and up to 1,120 Hz in the female group. The Chinese group had significantly higher RF than the Caucasian group. Once the effect of body size was compensated by adjusting for the ear canal and the middle ear volumes, the differences observed between the Caucasian and the Chinese groups were no longer significant for tympanometric parameters obtained at standard probe tone frequency of 226 Hz; however, the effect was still significant for SA obtained at higher probe tone frequencies (560, 630, 710, 800, and 900 Hz) and for RF. Applying the Caucasian norms to a group of mainly Caucasian adults with surgically confirmed otosclerosis resulted in improved overall test performance when compared with the combined Caucasian and Chinese norms and the Chinese only norms.
It seems that the body size plays a crucial factor in the observed differences between the Caucasian group and Chinese groups at a standard probe tone frequency of 226 Hz; however, other mechano-acoustical properties of the middle ear may contribute to these differences at higher probe tone frequencies. Findings of this study suggest that further research is needed to investigate the effects of body size on immittance measures with other ethnic groups. In the meantime, overall test performance may be improved by using a more homogenous norm when testing the Caucasian or Chinese individuals.