Πέμπτη 22 Σεπτεμβρίου 2016

A novel missense mutation in the C2C domain of otoferlin causes profound hearing impairment in an Omani family with auditory neuropathy.

A novel missense mutation in the C2C domain of otoferlin causes profound hearing impairment in an Omani family with auditory neuropathy.

Saudi Med J. 2016 Oct;37(10):1068-1075

Authors: Al-Wardy NM, Al-Kindi MN, Al-Khabouri MJ, Tamimi Y, Van Camp G

Abstract
OBJECTIVES: To identify genetic defects in an Omani family diagnosed with deafness. Methods: A cross-sectional association study was conducted at the Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoud, Oman and the Centre of Medical Genetics, University of Antwerp, Antwerp, Belgium between August 2010 and September 2014. Microsatellites markers for nine non-syndromic genes were used to genotype the defective locus using the extracted DNA from family members. Sanger sequencing method was used to identify the disease causative mutation. Eazy linkage 5.05 was used to calculate the logarithm of odds score. Lasergene suite was used to detect the mutation position, and Phyre2, SMART, Rasmol, and GOR IV were used to predict the effects of the defect on protein structure and function. Results: The disease was linked to markers located on chromosome-2 and covering the OTOF (DFNB9) gene. A novel missense mutation that changed nucleotide C to G at position c.1469 and consequently the amino acid Proline to Arginine (P490R) on exon 15 was detected. Protein modeling analysis revealed the impact of the mutation on protein structure and the relevant C2C domain. The mutation seems to create a new protein isoform homologous to the complement component C1q. Conclusion: These findings suggest that the mutation found in C2C domain of the OTOF gene is likely to cause deafness in the studied family reflecting the importance of C2 domains of otoferlin in hearing loss.

PMID: 27652356 [PubMed - as supplied by publisher]



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Cryopyrin-associated periodic syndrome in Australian children and adults: Epidemiological, clinical and treatment characteristics.

Cryopyrin-associated periodic syndrome in Australian children and adults: Epidemiological, clinical and treatment characteristics.

J Paediatr Child Health. 2016 Sep;52(9):889-895

Authors: Mehr S, Allen R, Boros C, Adib N, Kakakios A, Turner PJ, Rogers M, Zurynski Y, Singh-Grewal D

Abstract
AIM: Cryopyrin-associated periodic syndromes (CAPS) encapsulate three auto-inflammatory conditions, ranging in severity from mild (familial cold auto-inflammatory syndrome: FCAS), moderate (Muckle-Wells syndrome: MWS) and severe (neonatal onset multi-inflammatory disorder: NOMID). We aimed to describe the epidemiology, clinical features and outcomes of Australian children and adults with CAPS.
METHODS: Patients were identified and clinical data collected through a questionnaire sent during 2012-2013 to clinicians reporting to the Australian Paediatric Surveillance Unit and subscribing to the Australasian Societies for Allergy/Immunology, Rheumatology and Dermatology.
RESULTS: Eighteen cases of CAPS were identified (8 NOMID; 8 MWS, 2 FCAS); 12 in children <18 years of age. The estimated population prevalence of CAPS was 1 per million persons. Diagnostic delay was frequent, particularly in those with milder phenotypes (median diagnostic delay in MWS/FCAS 20.6 years compared with NOMID 2.1 years; P = 0.04). Common presenting features included urticaria (100%), periodic fever (78%), arthralgia (72%) and sensorineural hearing loss (61%). Almost all (90%) MWS patients had a family member similarly affected compared with none in the NOMID group (P = 0.004). A significant proportion of patients on anti-interleukin (IL)-1 therapy (n = 13) no longer had systemic inflammation. Only 50% with sensorineural hearing loss had hearing restored on anti-IL-1 therapy.
CONCLUSIONS: Although CAPS are rare, patients often endured prolonged periods of systemic inflammation. This is despite almost all MWS patients having family members with similar symptoms and children with NOMID presenting with chronic infantile urticaria associated with multi-system inflammation. Hearing loss in NOMID/MWS was frequent, and reversible in only 50% of cases.

PMID: 27650144 [PubMed - as supplied by publisher]



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Everyday Listening Performance of Children Before and After Receiving a Second Cochlear Implant: Results Using the Parent Version of the Speech, Spatial, and Qualities of Hearing Scale.

http:--pt.wkhealth.com-pt-pt-core-templa Related Articles

Everyday Listening Performance of Children Before and After Receiving a Second Cochlear Implant: Results Using the Parent Version of the Speech, Spatial, and Qualities of Hearing Scale.

Ear Hear. 2016 Jan-Feb;37(1):93-102

Authors: Galvin KL, Mok M

Abstract
OBJECTIVES: To evaluate change in individual children's performance in general areas of everyday listening following sequential bilateral implantation, and to identify the specific types of listening scenarios in which performance change occurred. The first hypothesis was that parent performance ratings for their child would be higher in the bilateral versus unilateral implant condition for each section of the speech, spatial and qualities of hearing scale for parents, viz.: speech perception, spatial hearing, and qualities of hearing. The second hypothesis was that the rating for the participant group would be higher in the bilateral condition for speech perception items involving group conversation or background noise, spatial hearing items, and qualities of hearing items focused on sound segregation or listening effort.
DESIGN: Children receiving sequential bilateral implants at the Royal Victorian Eye and Ear Hospital and fulfilling selection criteria (primarily no significant cognitive or developmental delays, and oral English language skills of child and parent sufficient for completing assessments) were invited to participate in a wider project evaluating outcomes. The assessment protocol for older children included the speech, spatial, and qualities of hearing scale for parents. All children (n = 20; ages 4 to 15 years) whose parents completed the scale preoperatively and at 24-months postoperatively were included in this study. Ratings obtained preoperatively in the unilateral implant condition (or unilateral implant plus hearing aid for 4 participants) were compared with those obtained postoperatively in the bilateral implant condition.
RESULTS: Bilateral ratings were significantly higher than unilateral ratings on the speech section for 12 children (W ≥ 7.0; p ≤ 0.03), on the spatial section for 13 children (W ≥ 15.0; p ≤ 0.03), and on the qualities of hearing section for 9 children (W ≥ 15.0; p ≤ 0.047). The difference between conditions was unrelated to time between implants or age at bilateral implantation (r ≤ 0.4; p ≥ 0.082). The median bilateral ratings for the participant group were higher for all eight speech perception items, including, as predicted, those involving group conversation and/or background noise (W ≥ 37.5; p ≤ 0.043). Also, as predicted, the median bilateral ratings for the participant group were higher for all six spatial hearing items (W ≥ 88.0; p ≤ 0.014), and for qualities of hearing items related to sound segregation (W ≥ 94.0; p ≤ 0.029), but not for those related to listening effort (W ≤ 92.0; p ≥ 0.112).
CONCLUSIONS: Seventy-five percentage of parents perceived change in their child's daily listening performance postoperatively, and 25% perceived change across all three listening areas. For the overall participant group, the parents perceived a change in performance in the majority of specific listening scenarios, although change was limited in the qualities of hearing section, including no change in listening effort. Previous research suggests postoperative change was likely due to the headshadow effect and improved spatial hearing. Additional contributions may have been made by binaural summation, redundancy, and unmasking. For these participants, differences between device conditions may have been limited by their relatively old age at implantation, delay between implants, and limited bilateral experience. These results will provide valuable information to families during preoperative counseling and postoperative discussions about expected progress and evident benefit.

PMID: 26418045 [PubMed - indexed for MEDLINE]



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Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment.

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Audiometric Characteristics of a Dutch DFNA10 Family With Mid-Frequency Hearing Impairment.

Ear Hear. 2016 Jan-Feb;37(1):103-11

Authors: van Beelen E, Oonk AM, Leijendeckers JM, Hoefsloot EH, Pennings RJ, Feenstra I, Dieker HJ, Huygen PL, Snik AF, Kremer H, Kunst HP

Abstract
OBJECTIVES: Mutations in EYA4 can cause nonsyndromic autosomal dominant sensorineural hearing impairment (DFNA10) or a syndromic variant with hearing impairment and dilated cardiomyopathy. A mutation in EYA4 was found in a Dutch family, causing DFNA10. This study is focused on characterizing the hearing impairment in this family.
DESIGN: Whole exome sequencing was performed in the proband. In addition, peripheral blood samples were collected from 23 family members, and segregation analyses were performed. All participants underwent otorhinolaryngological examinations and pure-tone audiometry, and 12 participants underwent speech audiometry. In addition, an extended set of audiometric measurements was performed in five family members to evaluate the functional status of the cochlea. Vestibular testing was performed in three family members. Two individuals underwent echocardiography to evaluate the nonsyndromic phenotype.
RESULTS: The authors present a Dutch family with a truncating mutation in EYA4 causing a mid-frequency hearing impairment. This mutation (c.464del) leads to a frameshift and a premature stop codon (p.Pro155fsX). This mutation is the most N-terminal mutation in EYA4 found to date. In addition, a missense mutation, predicted to be deleterious, was found in EYA4 in two family members. Echocardiography in two family members revealed no signs of dilated cardiomyopathy. Results of caloric and velocity step tests in three family members showed no abnormalities. Hearing impairment was found to be symmetric and progressive, beginning as a mid-frequency hearing impairment in childhood and developing into a high-frequency, moderate hearing impairment later in life. Furthermore, an extended set of audiometric measurements was performed in five family members. The results were comparable to those obtained in patients with other sensory types of hearing impairments, such as patients with Usher syndrome type IIA and presbyacusis, and not to those obtained in patients with (cochlear) conductive types of hearing impairment, such as DFNA8/12 and DFNA13.
CONCLUSIONS: The mid-frequency hearing impairment in the present family was found to be symmetric and progressive, with a predominantly childhood onset. The results of psychophysical measurements revealed similarities to other conditions involving a sensory type of hearing impairment, such as Usher syndrome type IIA and presbyacusis. The study results suggest that EYA4 is expressed in the sensory cells of the cochlea. This phenotypic description will facilitate counseling for hearing impairment in DFNA10 patients.

PMID: 26331839 [PubMed - indexed for MEDLINE]



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Τετάρτη 21 Σεπτεμβρίου 2016

FDA permits marketing of balloon device to treat persistent Eustachian tube dysfunction

The U.S. Food and Drug Administration has permitted marketing of a device that uses a small balloon to treat persistent Eustachian tube dysfunction (ETD), a condition in which pressure, pain or...

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FDA permits marketing of balloon device to treat persistent Eustachian tube dysfunction

The U.S. Food and Drug Administration has permitted marketing of a device that uses a small balloon to treat persistent Eustachian tube dysfunction (ETD), a condition in which pressure, pain or...

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FDA permits marketing of balloon device to treat persistent Eustachian tube dysfunction

The U.S. Food and Drug Administration has permitted marketing of a device that uses a small balloon to treat persistent Eustachian tube dysfunction (ETD), a condition in which pressure, pain or...

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