学术投稿

关键词:Next-generation sequencing, molecular diagnosis, Inherited non-syndromic hearing loss, Whole genome sequencing, Whole exome sequencing
摘要:Hearing loss is one of the most common birth defects, with inherited genetic defects play an important role, contributing to about 60% of deafness occurring in infants. However, hearing impairment is genetically heterogeneous, with both common and rare forms occurring due to mutations in estimated 500 genes. Due to the large number and presumably low mutation frequencies of those genes, it would be highly expensive and time-consuming to address this issue by conventional gene-by-gene Sanger sequencing. Next-generation sequencing is a revo-lutionary technology that allows the simultaneous screening of mutations in a large number of genes. It is cost effective compared to classical strategies of linkage analysis and direct sequencing when the number or size of genes is large, and thus has become a highly efficient strategy for identifying novel causative genes and mutations involved in heritable disease.In this review, we describe major NGS methodologies currently used for genetic disorders and highlight applications of these technologies in studies of molecular diagnosis and the discovery of genes implicated in non-syndromic hearing loss.
中华耳科学(英文版)杂志相关文献
  • Gap induced pre-pulse inhibition (Gap-PPI) of acoustic startle reflex has been used as a measurement of tinnitus in animal models. However, whether this test is sensitive to detect tinnitus in humans is still unclear. Based on the testing procedure used in animal studies, a human subject testing method was formulated and conducted to investigate if a similar result could be found in tinnitus patients. Audiologic and tinnitus assessments and acoustic startle reflex measurements were performed on seven tinnitus subjects and nine age matched subjects without tinnitus. There was no significant difference found between the control and tinnitus group on the Gap-PPI across the frequencies evaluated. The amplitude of the startle response in the tinnitus group with normal hearing thresholds was significantly higher than the control group and those with tinnitus and hearing loss. This preliminary result suggests that hyperexcitability in the central auditory system may be involved in tinnitus. There was no correlation between hearing thresholds and the increased amplitude of startle response.

    作者: 刊期: 2014年第03期

  • Hearing loss is one of the most common birth defects, with inherited genetic defects play an important role, contributing to about 60% of deafness occurring in infants. However, hearing impairment is genetically heterogeneous, with both common and rare forms occurring due to mutations in estimated 500 genes. Due to the large number and presumably low mutation frequencies of those genes, it would be highly expensive and time-consuming to address this issue by conventional gene-by-gene Sanger sequencing. Next-generation sequencing is a revo-lutionary technology that allows the simultaneous screening of mutations in a large number of genes. It is cost effective compared to classical strategies of linkage analysis and direct sequencing when the number or size of genes is large, and thus has become a highly efficient strategy for identifying novel causative genes and mutations involved in heritable disease.In this review, we describe major NGS methodologies currently used for genetic disorders and highlight applications of these technologies in studies of molecular diagnosis and the discovery of genes implicated in non-syndromic hearing loss.

    作者: 刊期: 2014年第03期

  • The study reports a case of a 5-year-old Chinese girl diagnosed with Kabuki make-up Syndrome (KMS). The patient showed classic KMS appearance: widely separated eyes, ectropion of lateral one-third lower eyelids, flat nasal tip, and prominent ears. Auditory features in this individual included bilateral severe sensorineural hearing loss and lack of 40 Hz AERP responses identified at 1 year of age. The individual received cochlear implant (CI) in the left ear when 5 years old, and rehabilitation after CI treatment were 3 in speech intelligibility and 5 in auditory performance. Thus, our findings suggest that cochlear implant may be helpful to restore hearing for individuals with Kabuki syndrome. Copyright ? 2015, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. All rights reserved.

    作者: 刊期: 2014年第03期

  • ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant, with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm. Three kinds of FDA approved cochlear implants support ECAP testing. This article is to summarize the clinical application of ECAP test. ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery. In recent years, ECAP thresholds are also used to estimate the T levels and C levels helping programming. However, correlation between ECAP thresholds and psychophysical thresholds is affected by many factors. So far, ECAPs cannot yet be a good indicator of post-operative hearing and speech performance.

    作者: 刊期: 2014年第03期

  • There is growing evidence suggests that noise-induced cochlear damage may lead to hyperexcitability in the central auditory system (CAS) which may give rise to tinnitus. However, the correlation between the onset of the neurophysiological changes in the CAS and the onset of tinnitus has not been well studied. To investigate this relationship, chronic electrodes were implanted into the auditory cortex (AC) and sound evoked activities were measured from awake rats before and after noise exposure. The auditory brainstem response (ABR) was used to assess the degree of noise-induced hearing loss. Tinnitus was evaluated by measuring gap-induced prepulse inhibition (gap-PPI). Rats were exposed monaurally to a high-intensity narrowband noise centered at 12 kHz at a level of 120 dB SPL for 1 h. After the noise exposure, all the rats developed either permanent (>2 weeks) or temporary (<3 days) hearing loss in the exposed ear(s). The AC amplitudes increased significantly 4 h after the noise exposure. Most of the exposed rats also showed decreased gap-PPI. The post-exposure AC enhancement showed a positive correlation with the amount of hearing loss. The onset of tinnitus-like behavior was happened after the onset of AC enhancement.

    作者: 刊期: 2014年第03期

  • 作者: 刊期: 2014年第03期

  • Objectives: To evaluate outcomes in treating carcinoma of external auditory canal (EAC) and to analysis factors which effect the prognosis of this disease.Methods: A retrospectively review of 16 patients treated for carcinoma of EAC at our department between April 2000 and April 2014 was conducted. All patients underwent surgical treatment and the diagnosis confirmed by pathological examination.Results: There were adenoid cystic carcinoma (ACC) in 8 patients, squamous cell carcinoma (SCC) in 5 patients, adenocarcinoma (AC) in 2 patients, and verrucous carcinoma (VC) in 1 patient. The tumors were classified as Stage I in 4 cases, Stage II in 2 cases, Stage III in 3 cases, and Stage IV in 7 cases. Five patients underwent extensive tumor resection (ETR), 2 patients underwent lateral temporal bone resection (LTBR), 5 patients underwent modified LTBR, 2 patients underwent subtotal temporal bone resection (STBR), and 2 patients underwent only open biopsy. Besides, adjunctive procedures, including neck dissection, parotidectomy and pinna resection were performed when indicated. Ten patients received postoperative radiotherapy. By the end of follow up, two patients had died of their disease, 2 lost to follow up, 2 survived with the disease, and the rest survived disease-free. The median follow-up period was 24 months.Conclusion: Complete tumor resection appears to be an effective treatment for carcinoma of the EAC. Patients with SCC seem to have worse prognosis than those with ACC. Radiation therapy seems less effective for the disease than surgical treatment.

    作者: 刊期: 2014年第03期

中华耳科学(英文版)杂志

中华耳科学(英文版)杂志

主管:解放军总医院

主办:解放军总医院耳鼻咽喉科研究所