A New Large Deletion in the DFNB1 Locus Causes Nonsyndromic Hearing Loss.

Mutations in the GJB2 gene encoding the gap junction protein connexin 26 are responsible for up to 30% of all cases of autosomal recessive nonsyndromic hearing impairment (HI) with prelingual onset in most populations. The corresponding locus DFNB1, located on chromosome 13q11-q12, is also affected by three distinct deletions. These deletions extended distally to GJB2, which remains intact. We report a novel large deletion in DFNB1 observed in a patient presenting profound prelingual HI. This deletion was observed in trans to a GJB2 mutated allele carrying the p.Val84Met (V84M) mutation and was shown to be associated with hearing loss. The deletion caused a false homozygosity of V84M in the proband. Quantification of alleles by quantitative fluorescent multiplex PCR (QFM-PCR) enabled us to study the breakpoints of the deletion. The deleted segment extended through at least 920kb and removed the three connexin genes GJA3, GJB2 and GJB6. The distal breakpoint inside intron 2 of CRYL1 gene differed from the breakpoints of the known DFNB1 deletions. This case highlights the importance of screening for large deletions in molecular studies of GJB2.

Functional Variants in NOS1 and NOS2A Are Not Associated with Progressive Hearing Loss in Ménière's Disease in a European Caucasian Population

Hearing loss in Meniere's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, wed genotyped three functional variants of NOS1 (rs41279104,rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets(273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p =0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and and NOS2A do not confer susceptibility for MD.

An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss.

Building on our discovery that mutations in the transmembrane serine protease, TMPRSS3, cause nonsyndromic deafness, we have investigated the contribution of other TMPRSS family members to the auditory function. To identify which of the 16 known TMPRSS genes had a strong likelihood of involvement in hearing function, three types of biological evidence were examined: 1) expression in inner ear tissues; 2) location in a genomic interval that contains a yet unidentified gene for deafness; and 3) evaluation of hearing status of any available Tmprss knockout mouse strains. This analysis demonstrated that, besides TMPRSS3, another TMPRSS gene was essential for hearing and, indeed, mice deficient for Hepsin (Hpn) also known as Tmprss1 exhibited profound hearing loss. In addition, TMPRSS2, TMPRSS5, and CORIN, also named TMPRSS10, showed strong likelihood of involvement based on their inner ear expression and mapping position within deafness loci PKSR7, DFNB24, and DFNB25, respectively. These four TMPRSS genes were then screened for mutations in affected members of the DFNB24 and DFNB25 deafness families, and in a cohort of 362 sporadic deaf cases. This large mutation screen revealed numerous novel sequence variations including three potential pathogenic mutations in the TMPRSS5 gene. The mutant forms of TMPRSS5 showed reduced or absent proteolytic activity. Subsequently, TMPRSS genes with evidence of involvement in deafness were further characterized, and their sites of expression were determined. Tmprss1, 3, and 5 proteins were detected in spiral ganglion neurons. Tmprss3 was also present in the organ of Corti. TMPRSS1 and 3 proteins appeared stably anchored to the endoplasmic reticulum membranes, whereas TMPRSS5 was also detected at the plasma membrane. Collectively, these results provide evidence that TMPRSS1 and TMPRSS3 play and TMPRSS5 may play important and specific roles in hearing.

Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease.

Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.

Surdités légères et surdités unilatérales chez l'enfant: quelle importance [Minimal or unilateral hearing loss in children: is it a problem?].

The word "minimal" or "mild" hearing loss seems to imply that their effects are mild or negligible. The literature supports that they can have a significant impact on educative end educational development of young children and contribute to problems in fields of social function, communication and educational achievement. Unilateral hearing loss in children has been considered for long to be of little consequence. In fact it causes problems in speech and language development, speech understanding, especially in noisy environments, and school results. Early diagnosis, follow-up during preschool and school ages are mandatory.

Hearing loss in Adult Women with Turner Syndrome

L'objectiu d'aquest estudi és definir els patrons d’hipoacúsia en dones amb Síndrome de Turner i els possibles factors que poden afavorir el desenvolupament d’hipoacúsia neurosensorial en dones adultes amb Síndrome de Turner. Es va trobar que més de la meitat de les dones amb Sindrome de Turner presenten hipoacúsia a l’audiometria, confirmat pels potencials evocats auditius de tronc; la hipoacúsia neurosensorial és el tipus de pèrdua d'audició més freqüent entre dones de mitjana edat amb síndrome de Turner i l'edat, el cariotip i la història prèvia d'otitis mitja recurrent són possibles factors de risc per l’aparició d’hipoacúsia en aquestes pacients.

Classification and hearing evolution of patients with sudden sensorineural hearing loss

The aim of this study was to analyze clinical aspects, hearing evolution and efficacy of clinical treatment of patients with sudden sensorineural hearing loss (SSNHL). This was a prospective clinical study of 136 consecutive patients with SSNHL divided into three groups after diagnostic evaluation: patients with defined etiology (DE, N = 13, 10%), concurrent diseases (CD, N = 63, 46.04%) and idiopathic sudden sensorineural hearing loss (ISSHL, N = 60, 43.9%). Initial treatment consisted of prednisone and pentoxifylline. Clinical aspects and hearing evolution for up to 6 months were evaluated. Group CD comprised 73% of patients with metabolic decompensation in the initial evaluation and was significantly older (53.80 years) than groups DE (41.93 years) and ISSHL (39.13 years). Comparison of the mean initial and final hearing loss of the three groups revealed a significant hearing improvement for group CD (P = 0.001) and group ISSHL (P = 0.001). Group DE did not present a significant difference in thresholds. The clinical classification for SSNHL allows the identification of significant differences regarding age, initial and final hearing impairment and likelihood of response to therapy. Elevated age and presence of coexisting disease were associated with a greater initial hearing impact and poorer hearing recovery after 6 months. Patients with defined etiology presented a much more limited response to therapy. The occurrence of decompensated metabolic and cardiovascular diseases and the possibility of first manifestation of auto-immune disease and cerebello-pontine angle tumors justify an adequate protocol for investigation of SSNHL.

Canonical syllable reduplication in infants with sensorineural hearing loss. 'Reduplicación y mezcla de sílabas balbuceadas en niños con hipoacusia'.

Resumen en español. Resumen basado en el de la publicación

A survey of the distribution of information regarding hearing loss to parents by hospitals and pediatricians in the St. Louis area

This paper discusses a survey undertaken to review information on hearing loss distributed by St. Louis area hospitals and pediatricians.

Speech intelligibility in noise-induced hearing loss: effects of high-frequency compensation

This dissertation examines the frequency response that results in the maximum level of speech intelligibility for persons with noise-induced hearing loss.

Effect of amplification bandwidth on intelligibility of several different speech samples for a listener with sensorineural hearing loss

This paper examines the effect of amplification bandwidth on speech intelligibility using multiple speech samples.

Effect of auditory processing on the preference of monaural amplification for adults with symmetrical hearing loss

The purpose of this project was to determine if subjects with symmetrical hearing loss who prefer a monaural hearing aid fit to a binaural hearing aid fit may demonstrate an auditory processing disorder causing them to experience binaural interference when fit binaurally.

An exploration of the role of narrative skills in higher-level reading comprehension of teenagers with hearing loss

This Study examines the relationship between scores on adolescents’ self-generated narratives and standardized reading-comprehension scores. This relationship is also compared with the more simple language metrics: vocabulary and syntax.

Role of alpha synuclein in noise induced hearing loss

The recent discovery of the contribution of alpha synuclein in the auditory system prompted further investigation of its functional role. Auditory brainstem response (ABR) and gap detection testing were completed on wild-type and transgenic M83 mice to assess the role of alpha synuclein in noise-induced hearing loss and central auditory function.

Implications of newborn hearing screening: counseling parents of newborns with hearing loss

This paper reviews parental reactions to their newborn newly diagnosed with a hearing loss.