Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report two cases in which the probands presented with deafness and a family history of a dominantly inherited auditory pigmentary syndrome, yet the cause of deafness in each proband was not associated with the pigmentary abnormalities but was a result of mutations in SLC26A4, the gene mutated in Pendred's syndrome. The first case is a young woman with congenital sensorineural hearing loss and a family history of piebaldism. Despite showing no pigmentary abnormalities, the proband was found to harbor the same KIT mutation as her relatives affected by piebaldism, as well as two mutations in the SLC26A4 gene. In the second case, 2-year-old identical twin boys born to deaf parents presented with congenital sensorineural deafness and an extensive maternal family history of Waardenburg's syndrome type I (WSI). Their father had recessively inherited deafness associated with dilated vestibular aqueducts and a clinical diagnosis of Pendred's syndrome was made in him, which was confirmed molecularly. As the twin boys did not have features of WSI, both the mother and children were tested for mutations in SLC26A4 which showed the mother to be a carrier of a single mutation and both boys to be compound heterozygotes, illustrating pseudodominant inheritance of the condition.
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PMID:Molecular heterogeneity in two families with auditory pigmentary syndromes: the role of neuroimaging and genetic analysis in deafness. 1509 45

We compared the output of two electronic middle ear implants: the Otologics MET device and the Vibrant Soundbridge device. Both devices were programmed in the linear amplification mode. Aided minus unaided sound pressure levels recorded in the ear canal (objective gain) were compared to unaided minus aided soundfield thresholds (functional gain) in 13 patients with severe sensorineural hearing loss. In addition, input/output characteristics were studied with the help of ear canal measurements. Objective gain was consistently lower than functional gain, with wide variation between patients and frequencies. Using input/output data measured in the ear canal in combination with functional gain data, the mean maximum output of the two devices was estimated, expressed in dB SPL. In comparison to NAL-R target values, (functional) gain was adequate; however, the maximum output was low, especially for the Vibrant Soundbridge device.
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PMID:Gain and maximum output of two electromagnetic middle ear implants: are real ear measurements helpful? 1511 65

In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKCbetaI was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKCbetaI. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKCbetaI activation represents a key factor for the protection of the integrity of neural elements in the cochlea.
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PMID:Activation of protein kinase CbetaI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons. 1617 9

The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke's syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3. Within a total of 124 independent pedigrees, 39 (71 patients) were identified to carry 25 different mutations of TWIST 1 including 14 novel mutations, to which six whole gene deletions were added. The 71 patients were compared with 42 subjects from 24 pedigrees carrying the Pro250Arg mutation in FGFR3 and 65 subjects from 61 pedigrees without a detectable mutation. Classical SCS associated with a TWIST 1 mutation could be separated phenotypically from the Muenke phenotype on the basis of the following features: low-set frontal hairline, gross ptosis of eyelids, subnormal ear length, dilated parietal foramina, interdigital webbing, and hallux valgus or broad great toe with bifid distal phalanx. Functional differences were even more important: intracranial hypertension as a consequence of early progressive multisutural fusion was a significant problem in SCS only, while mental delay and sensorineural hearing loss were associated with the Muenke's syndrome. Contrary to previous reports, SCS patients with complete loss of one TWIST allele showed normal mental development.
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PMID:Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. 1625 95

Sensorineural hearing loss is often associated with damage of cochlear hair cells and/or of the neurons of the auditory pathway. This damage can result from a variety of causes, e.g. genetic disorders, aging, exposure to certain drugs such as aminoglycosides, infectious disease and intense sound overexposure. Intracellular events that mediate aspects of aminoglycoside-mediated damage to hair cells have been partially unraveled. Several independent research groups have demonstrated a crucial role of mitogen-activated protein kinase signaling in aminoglycoside-induced ototoxicity. Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus. Jun N-terminal kinases, members of the mitogen-activated protein kinase family, are strongly activated in cell culture conditions by stress inducing stimuli, including ultraviolet light, heat shock and tumor necrosis factor; therefore they are also referred to as stress-activated protein kinases. In hair cells aminoglycoside treatment was shown to activate the Jun N-terminal kinase signaling pathway. Activation of Jun N-terminal kinase leads to phosphorylation and thereby activation of transcription factors and consequently to altered gene expression. There are many nuclear Jun N-terminal kinase substrates including c-Jun, ATF-2, and Elk-1 proteins. One of the downstream targets of Jun N-terminal kinase is the transcription factor activating protein-1. Activating protein-1 is a dimeric complex composed of members of the Fos and Jun proteins. A variety of different stimuli is known to induce activating protein-1 activity. Induction of activating protein-1 is thought to play a central role in reprogramming gene expression in response to external stimuli. In this study we have analyzed the effect of gentamicin treatment on the downstream targets of Jun N-terminal kinase. Our results demonstrate that gentamicin treatment of explants of organ of Corti results in increased activating protein-1 binding activity. The main component of these activating protein-1 complexes is the c-Fos protein. Moreover, we show that the activating protein-1 induction is transient and occurs exclusively in hair cells of rat organ of Corti explants.
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PMID:Alteration of activator protein 1 DNA binding activity in gentamicin-induced hair cell degeneration. 1633 90

Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings in Muenke syndrome. To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. We reviewed audiograms from an additional 13 patients with Muenke syndrome. A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss. This pattern of hearing loss was not previously recognized as characteristic of Muenke syndrome. We also report on feeding and swallowing difficulties in children with Muenke syndrome. Combining 312 reported cases of Muenke syndrome with data from the nine NIH patients, we found that females with the Pro250Arg mutation were significantly more likely to be reported with craniosynostosis than males (P < 0.01). Based on our findings, we propose that the clinical management should include audiometric and developmental assessment in addition to standard clinical care and appropriate genetic counseling.
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PMID:Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature. 1800 Sep 76

This report documents a case with primary amenorrhea associated with sensorineural hearing loss and anosmia. The patient presented at 18 years of age with minimal sexual development and no prior menses. Her mother also presented late onset menarche, hearing loss and anosmia, and her father was also affected with hearing loss. A chromosome analysis of the patient showed 46, XX. Basal FSH and LH levels were in normal range, but the serum estradiol level was low. A serum estradiol elevation and follicular development were recognized after the injection of human menopausal gonadotropin. Genomic DNA sequencing of FSHB, FSHR, KAL1, FGFR1, PROK2 and PROKR2 did not show any mutation. Audiometry showed severe bilateral sensorineural hearing loss and smell testing confirmed a severely impaired olfactory function. These findings probably suggested a case of delayed puberty associated with sensorineural hearing loss and anosmia.
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PMID:Primary amenorrhea in an 18-year-old Japanese female with sensorineural hearing loss and anosmia: a new sydrome? 1848 May 58

In recent years semi-implantable hearing aids have become an established option in the treatment of sensorineural hearing loss. In Germany two semi-implantable systems are available, namely the MedEl Soundbridge system and the Otologics MET system, both of which are active middle ear implants. Since 1996 almost 3,500 Soundbridge systems and 300 MET systems have been implanted world-wide. The majority of patients who have received semi-implantable hearing aids consider them to be superior to conventional hearing aids in many respects. Reported benefits include improved speech intelligibility (especially in noise), better sound quality, a more natural sounding own voice and the general advantages of an open ear canal. Implantable hearing systems can be used for a wider range of indications than conventional hearing aids. They are particularly useful in the treatment of patients with high-frequency hearing loss and patients with combined hearing loss. An analysis of the hearing outcomes that have thus far been reported for all patients with a hearing implant shows an average improvement in the hearing threshold by 15 dB, which corresponds to an improvement in hearing of more than 30%. As a consequence semi-implantable hearing systems are an excellent addition to the existing range of conventional hearing aids.
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PMID:[Semi-implantable hearing aids for sensorineural hearing loss and combined hearing loss: experiences at the German Armed Forces Hospital in Ulm]. 1924 25

Middle ear implants overcome some of the common problems of conventional hearing aid technology, such as feedback, signal distortion, ear canal occlusion and associated issues. The Otologics MET Carina, Boulder, CO, USA, is a fully implantable hearing prosthesis designed to address the amplification needs of adults (> 18 years of age), with moderate to severe sensorineural hearing loss and normal middle ears, providing a mechanical direct stimulation of middle ear ossicles. Recently, it has been successfully used also in patients with conductive hearing loss. In the present report, personal surgical and clinical experience with the fully implantable Carina is described in 5 adults with moderate to severe sensorineural hearing loss, operated upon between November 2007 and May 2008 in the ENT Unit, University of Pisa. Mean follow-up was 10.2 months of device use (range 7-13). Surgery was performed under general anaesthesia, in approximately 3 hours, with no surgical complications in any of the patients. In these 5 cases, no significant post-operative variation was observed in hearing thresholds, either for air or bone conduction, indicating absence of surgical damage to the cochlea. All patients showed improvements in hearing thresholds, in free field and in speech perception abilities, with the device functioning, moreover, they reported subjective benefits. With regard to post-operative adverse effects, no cases of extrusion of the device, device failure, loss of external communication or increased charging times were observed. Problems of feedback noise occurred, which were resolved with minor fitting adjustments in 4 cases, while a second operation was required to change the microphone position in the other patient. The present results, in agreement with those reported in the literature, confirm that the Otologics MET Carina is viable treatment for moderate to severe sensorineural hearing loss and, in selected cases, may represent an alternative to conventional hearing aids.
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PMID:Fully implantable Otologics MET Carina device for the treatment of sensorineural hearing loss. Preliminary surgical and clinical results. 2011 17

Sensorineural hearing loss (SNHL) produces deficits in speech comprehension in noise that primarily are due to impairments in identifying consonants. Here, we describe the California Syllable Test (CaST) that quantifies the identification of common American English consonants. In experiment I, 16 young subjects with normal hearing identified 720 consonant-vowel-consonant (CVC) syllables in three test sessions. Consonants were identified slightly more accurately in words than nonsense syllables, and small interactions were found between the processing of initial and final consonants. Consonant-identification performance correlated strongly with sentence reception thresholds (SeRTs) measured with both the Hearing in Noise Test and QuickSIN (Etymotic Research; Elk Grove Village, Illinois). At SeRTs, subjects with normal hearing could identify 32.5% of consonants in isolated CVCs. In experiment II, a patient with moderate SNHL showed large elevations in consonant-identification thresholds and smaller elevations in SeRTs. At SeRT levels, the patient could identify only 12.5% of consonants in isolated CVCs, indicating that sentence comprehension relied disproportionately on vowel cues and semantic constraints. Consonant-profile analysis revealed disproportional impairments in identifying consonants dependent on high-frequency acoustic cues. Consonant confusion analysis revealed a reorganization of consonant per ception. The CaST is a promising tool for evaluating consonant-specific processing deficits in patients with hearing impairment.
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PMID:Measuring consonant identification in nonsense syllables, words, and sentences. 2066 50


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