Mutation of SLC9A1, encoding the major Na⁺/H⁺ exchanger, causes ataxia-deafness Lichtenstein-Knorr syndrome.

Lichtenstein-Knorr syndrome is an autosomal recessive condition that associates sensorineural hearing loss and cerebellar ataxia. Here, we report the first identification of a gene involved in Lichtenstein-Knorr syndrome. By using a combination of homozygosity mapping and whole-exome sequencing, we identified the homozygous p.Gly305Arg missense mutation in SLC9A1 that segregates with the disease in a large consanguineous family. Mutant glycine 305 is a highly conserved amino acid present in the eighth transmembrane segment of all metazoan orthologues of NHE1, the Na(+)/H(+) exchanger 1, encoded by SLC9A1. We demonstrate that the p.Gly305Arg mutation causes the near complete de-glycosylation, mis-targeting and loss of proton pumping activity of NHE1. The comparison of our family with the phenotypes of spontaneous and knockout Slc9a1 murine models demonstrates that the association between ataxia and hearing loss is caused by complete or near complete loss of function of NHE1 and altered regulation of pHi in the central nervous system.

Effect of l-Arginine in One Patient with Peroxisome Biogenesis Disorder due to PEX12 Deficiency.

Peroxisome biogenesis disorders (PBD) are a heterogeneous group of disorders due to PEX genes mutations, with a broad clinical spectrum comprising severe neonatal disease to mild presentation. Recently, Berendse et al reported an improvement of peroxisomal functions with l-arginine supplementation in fibroblasts with specific mutations of PEX1, PEX6, and PEX12. We report the first treatment by l-arginine in a patient homozygous for the specific PEX12 mutation shown to be l-arginine responsive in fibroblasts. We described the effect of l-arginine on biochemical (decrease of some plasma peroxisomal parameters) and neurophysiological (improvement of deafness) parameters. Some subjective clinical effects have also been observed (no more sialorrhea, behavior improvement). More studies are needed to assess the efficacy of l-arginine in some PBD patients with specific mutations.

Quality of life and audiologic performance through the ability to phone of cochlear implant users.

This study aimed to evaluate the impact of cochlear implantation on quality of life (QoL), using general and cochlear implant (CI) specific questionnaires and to determine the relationship of phone ability with QoL, speech recognition abilities and tinnitus. Twenty-six adult volunteers with a post-lingual profound deafness, unilaterally implanted with a CI, were included in this study. All subjects had used a CI for at least 1 year. The Glasgow benefit inventory (GBI) and Nijmegen cochlear implant questionnaire (NCIQ) were administered to assess QoL. Speech recognition was tested using phonemic Lafon's lists. The subjective tinnitus severity scale (STSS) questionnaire was used to determine the effects of tinnitus. CI users were split into four groups according to their phone ability. There was an improvement in QoL after cochlear implantation. The NCIQ showed significant (p < 0.001) improvements in the total score and in all subdomains after CI. A significant relationship between phone ability, QoL and speech recognition was found. Improving phone ability led to higher QoL (p < 0.05) and speech recognition (p < 0.01) scores. The CI use decreased significantly the occurrence of tinnitus, but its severity was not correlated with QoL. Post-surgery assessment should include speech recognition measures and QoL evaluation. The NCIQ appeared more effective than the GBI in its ability to detect improvements in QoL. Assessing phone ability represents an easy and fast approach to evaluate hearing performances and QoL, and may reflect global outcomes of CI.

The Development of the "Telislife" Questionnaire for the Evaluation of Telephone Use in Cochlear Implant Users.

Purpose For cochlear implant users, the ability to use the telephone is often seen as an important landmark during rehabilitation and an indicator of cochlear implant benefit. The goal of this study was to develop a short questionnaire exploring the ability to use the telephone in cochlear implant users, named Telislife, and test it in a group of experienced users. Method This prospective multicenter study was based on the completion of self-administrated questionnaires. The Telislife includes 20 items using a 5-point Likert scale for answers. Speech recognition scores were obtained with monosyllabic word lists at 70 dB HL. Quality of life was evaluated with the Nijmegen Cochlear Implant Questionnaire. This study included 55 adult patients wearing a cochlear implant for over 1 year. Results The Telislife questionnaire showed excellent reliability (Cronbach's α = .91). A significant correlation was found between Telislife scores and Nijmegen Cochlear Implant Questionnaire scores (r = .69, p < .001) and speech recognition scores (r = .35, p = .007). Conclusion Given significant correlations between Telislife scores and both speech recognition and quality of life and given its short form, the Telislife questionnaire appears to be a reliable tool to evaluate cochlear implant outcomes in clinical practice. Supplemental Material https://doi.org/10.23641/asha.13322873.

Cognitive Abilities and Quality of Life After Cochlear Implantation in the Elderly.

OBJECTIVE: To evaluate quality of life (QoL) and cognitive function in elderly patients with cochlear implants relative to auditory improvement, using geriatric validated scales. STUDY DESIGN: Prospective observational study. SETTING: A tertiary referral center for cochlear implantation (CI) and a geriatric center in Nancy, France. PATIENTS: Sixteen consecutive patients were included, from 65 to 80 years old, with postlingual severe-to-profound deafness. MAIN OUTCOME MEASURES: Evaluations were conducted before and at 6 and 12 months after cochlear implant surgery. A monosyllabic word recognition test was used to measure speech perception. QoL was evaluated by the World Health Organization Quality of Life Assessment for elderly people; cognitive function was evaluated by the Mini-Mental State Examination; depression was evaluated by the Hamilton Scale; autonomy was evaluated by the Instrumental Activities of Daily Living. RESULTS: Speech intelligibility evolved from 10% before surgery to 63% and 69% at 6 and 12 months after cochlear implant activation, respectively. QoL showed significant improvement in sensory abilities. The Mini-Mental State Examination evaluations remained stable and executive functions tended to improve. Autonomy improved significantly. CONCLUSION: Cochlear implantation improves autonomy and the QoL in the elderly. Cognitive functions are not influenced by surgery, but executive functions appear to benefit from implantation. Age should not be a limiting factor, and cochlear implantation can be proposed as an efficient treatment for severe-to-profound hearing loss in the elderly.

Effects of Unilateral Cochlear Implantation on Balance Control and Sensory Organization in Adult Patients with Profound Hearing Loss.

Many studies were interested in the consequence of vestibular dysfunction related to cochlear implantation on balance control. This pilot study aimed to assess the effects of unilateral cochlear implantation on the modalities of balance control and sensorimotor strategies. Posturographic and vestibular evaluations were performed in 10 patients (55 ± 20 years) with profound hearing loss who were candidates to undergo unilateral multichannel cochlear implantation. The evaluation was carried out shortly before and one year after surgery. Posturographic tests were also performed in 10 age-matched healthy participants (63 ± 16 years). Vestibular compensation was observed within one year. In addition, postural performances of the patients increased within one year after cochlear implantation, especially in the more complex situations, in which sensory information is either unavailable or conflicting. Before surgery, postural performances were higher in the control group compared to the patients' group. One year after cochlear implantation, postural control was close to normalize. The improvement of postural performance could be explained by a mechanism of vestibular compensation. In addition, the recovery of auditory information which is the consequence of cochlear implantation could lead to an extended exploration of the environment possibly favoring the development of new balance strategies.

Who are the "occasional" snorers?

STUDY OBJECTIVES: To assess the prevalence of occasional snoring in a group of middle-aged men, and to compare anthropometric variables and prevalence of sleep-related symptoms of subjects who occasionally snore with those of other snoring categories. DESIGN: A field survey of a sample of middle-aged men in France. PARTICIPANTS: Male employees of a local university and subjects from the community attending a preventive medicine center. Participation rate was 93.5%. MEASUREMENTS: Anthropometric variables were recorded in 499 subjects aged 23 to 66 years (mean, 44.3 years). The subjects completed a standard sleep questionnaire and were classified according to the snoring frequency as never, rarely, sometimes, occasional, several nights per week, and every night. The subjects who snore occasionally represented 8.6% of the total. RESULTS: The anthropometric data of subjects who snore occasionally were similar to those of subjects who habitually snore. When compared with subjects who do not snore, older age and a larger neck girth were significant. Subjects who snore occasionally were also significantly more often subjects who snore loudly, and tended more frequently to have breathing stops during sleep. CONCLUSIONS: Our epidemiologic study shows that approximately 9% of a sample of middle-aged men snore occasionally. Subjects who snore occasionally have anthropometric characteristics close to those of subjects who snore habitually. The prevalence of the main sleep-related symptoms is between that of subjects who do not snore and of subjects who snore habitually. In an epidemiologic setting, inclusion of subjects who snore occasionally as subjects who do not snore or subjects who snore habitually will lead to bias. The present results suggest they should be identified and considered as a separate category.

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

BACKGROUND: Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. METHODS: We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). RESULTS: Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. CONCLUSIONS: Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.