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OtoRhinoLaryngology by Sfakianakis G.Alexandros Sfakianakis G.Alexandros,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,tel : 00302841026182,00306932607174
Related Articles |
Rare compound heterozygosity involving dominant and recessive mutations of GJB2 gene in an assortative mating hearing impaired Indian family.
Eur Arch Otorhinolaryngol. 2016 Aug 1;
Authors: Pavithra A, Chandru J, Jeffrey JM, Karthikeyen NP, Srisailapathy CR
Abstract
Connexin 26 (Cx-26), a gap junction protein coded by GJB2 gene, plays a very important role in recycling of potassium ions, one of the vital steps in the mechanotransduction process of hearing. Mutations in the GJB2 gene have been associated with both autosomal recessive as well as dominant nonsyndromic hearing loss. As Cx-26 is linked with skin homeostasis, mutations in this gene are sometimes associated with syndromic forms of hearing loss showing skin anomalies. We report here a non consanguineous assortatively mating hearing impaired family with one of the hearing impaired partners, their hearing impaired sibling and hearing impaired offspring showing compound heterozygosity in the GJB2 gene, involving a dominant mutation p.R184Q and two recessive mutations p.Q124X and c.IVS 1+1G>A in a unique triallelic combination. To the best of our knowledge, this is the first report from India on p.R184Q mutation in the GJB2 gene associated with rare compound heterozygosity showing nonsyndromic presentation.
PMID: 27481527 [PubMed - as supplied by publisher]
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Outcomes of evaluation and testing of 660 individuals with hearing loss in a pediatric genetics of hearing loss clinic.
Am J Med Genet A. 2016 Aug 2;
Authors: Mehta D, Noon SE, Schwartz E, Wilkens A, Bedoukian EC, Scarano I, Crenshaw EB, Krantz ID
Abstract
Hearing loss is a relatively common condition in children, occurring in approximately 2 out of every 1,000 births with approximately 50% of reported diagnoses having a primary genetic etiology. Given the prevalence and genetic component of hearing loss, coupled with a trend toward early diagnosis with the institution of universal newborn hearing screening, The Genetics of Hearing Loss Clinic was established at The Children's Hospital of Philadelphia to manage the diagnosis, testing, and genetic counseling for individuals and families. This paper described a cohort of 660 individuals with a diagnosis of hearing loss evaluated between July 2008 and July 2015 in the Genetics of Hearing Loss Clinic. To elucidate the cause of hearing loss in this cohort for better management and prognostication, testing included single nucleotide polymorphism chromosomal microarray, hearing loss next generation sequencing panel, and additional clinical tests inclusive of thyroid and renal function studies, temporal bone magnetic resonance imaging, and electrocardiogram. Of those evaluated, most had bilateral sensorineural hearing loss, occurring in 489/660 (74%). Additionally, 612/660 (93%) of patients presented with a nonsyndromic form of hearing loss (no other observed clinical findings at the time of exam), of which pathogenic mutations in GJB2 were most prevalent. Of the individuals with syndromic manifestations (48/660), Usher and Waardenburg syndrome were most commonly observed. A family history of hearing loss (first degree relative) was present in 12.6% of families with available information. Through molecular analyses, clinical examination, and laboratory testing, a definitive etiologic diagnosis was established in 157/660 (23.8%) of individuals. © 2016 Wiley Periodicals, Inc.
PMID: 27480936 [PubMed - as supplied by publisher]
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Two‑gene mutation in a single patient: Biochemical and functional analysis for a correct interpretation of exome results.
Mol Med Rep. 2015 Oct;12(4):6128-32
Authors: Bianco AM, Faletra F, Vozzi D, Girardelli M, Knowles A, Tommasini A, Zauli G, Marcuzzi A
Abstract
Next-generation sequencing (NGS) has generated a large amount of sequence data with the requirement of frequent critical revisions of reported mutations. This innovative tool has proved to be effective in detecting pathogenic mutations; however, it requires a certain degree of experience to identify incidental findings. In the present study, whole exome sequencing analysis was performed for the molecular diagnosis and correct genotype/phenotype correlation between parents and a patient presenting with an atypical phenotype. In addition, mevalonic acid quantification and frequency analysis of detected variants in public databases and X‑chromosome inactivation (XCI) studies on the patient's mother were performed. V377I as well as the S135L mutations were identified on the mevalonate kinase deficiency gene and the levels of mevalonic acid in the patient were 5,496 µg/ml. A D59G variation, reported in ESP6500 in two healthy individuals, was found on the Martin Probst syndrome gene (RAB40AL). Based on XCI studies on the patient's mother, it is likely that RAB40AL escapes XCI, while still remaining balanced. In conclusion, the results of the present study indicated that the Martin Probst syndrome is an X‑linked condition, which is probably not caused by RAB40AL mutations. Although NGS is a powerful tool to identify pathogenic mutations, the analysis of genetic data requires expert critical revision of all detected variants.
PMID: 26300074 [PubMed - indexed for MEDLINE]
The hidden Markov models have been widely applied to systems with sequential data. However, the conditional independence of the state outputs will limit the output of a hidden Markov model to be a piecewise constant random sequence, which is not a good approximation for many real processes. In this paper, a high-order hidden Markov model for piecewise linear processes is proposed to better approximate the behavior of a real process. A parameter estimation method based on the expectation-maximization algorithm was derived for the proposed model. Experiments on speech recognition of noisy Mandarin digits were conducted to examine the effectiveness of the proposed method. Experimental results show that the proposed method can reduce the recognition error rate compared to a baseline hidden Markov model.
This study investigated how speech recognition during speech-on-speech masking may be impaired due to the interaction between amplitude modulations of the target and competing talker. Young normal-hearing adults were tested in a competing talker paradigm where the target and/or competing talker was processed to primarily preserve amplitude modulation cues. Effects of talker sex and linguistic interference were also examined. Results suggest that performance patterns for natural speech-on-speech conditions are largely consistent with the same masking patterns observed for signals primarily limited to temporal amplitude modulations. However, results also suggest a role for spectral cues in talker segregation and linguistic competition.