A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report.

Related Articles

A novel mutation of the MITF gene in a family with Waardenburg syndrome type 2: A case report.

Exp Ther Med. 2016 Apr;11(4):1516-1518

Authors: Shi Y, Li X, Ju D, Li Y, Zhang X, Zhang Y

Abstract
Waardenburg syndrome (WS) is an autosomal dominant disorder with varying degrees of sensorineural hearing loss, and accumulation of pigmentation in hair, skin and iris. There are four types of WS (WS1-4) with differing characteristics. Mutations in six genes [paired box gene 3 (PAX3), microphthalmia-associated transcription factor (MITF), endothelin 3 (END3), endothelin receptor type B (EDNRB), SRY (sex determining region Y)-box 10 (SOX10) and snail homolog 2 (SNAI2)] have been identified to be associated with the various types. This case report describes the investigation of genetic mutations in three patients with WS2 from a single family. Genomic DNA was extracted, and the six WS-related genes were sequenced using next-generation sequencing technology. In addition to mutations in PAX3, EDNRB and SOX10, a novel heterozygous MITF mutation, p.Δ315Arg (c.944_946delGAA) on exon 8 was identified. This is predicted to be a candidate disease-causing mutation that may affect the structure and function of the enzyme.

PMID: 27073475 [PubMed - as supplied by publisher]

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1Na7Vq1
via IFTTT

New insights in the interpretation of array-CGH: autism spectrum disorder and positive family history for intellectual disability predict the detection of pathogenic variants.

Related Articles

New insights in the interpretation of array-CGH: autism spectrum disorder and positive family history for intellectual disability predict the detection of pathogenic variants.

Ital J Pediatr. 2016;42(1):39

Authors: Cappuccio G, Vitiello F, Casertano A, Fontana P, Genesio R, Bruzzese D, Ginocchio VM, Mormile A, Nitsch L, Andria G, Melis D

Abstract
BACKGROUND: Array-CGH (aCGH) is presently used into routine clinical practice for diagnosis of patients with intellectual disability (ID), multiple congenital anomalies (MCA), and autism spectrum disorder (ASD). ACGH could detect small chromosomal imbalances, copy number variations (CNVs), and closely define their size and gene content. ACGH detects pathogenic imbalances in 14-20 % of patients with ID. The aims of this study were: to establish clinical clues potentially associated with pathogenic CNVs and to identify cytogenetic indicators to predict the pathogenicity of the variants of uncertain significance (VOUS) in a large cohort of paediatric patients.
METHODS: We enrolled 214 patients referred for either: ID, and/or ASD and/or MCA to genetic services at the Federico II University of Naples, Department of Translational Medicine. For each patient we collected clinical and imaging data. All the patients were tested with aCGH or as first-tier test or as part of a wider diagnostic work-up.
RESULTS: Pathologic data were detected in 65 individuals (30 %) and 46 CNVs revealed a known syndrome. The pathological CNVs were usually deletions showing the highest gene-dosage content. The positive family history for ID/ASD/MCA and ASD were good indicators for detecting pathological chromosomal rearrangements. Other clinical features as eyes anomalies, hearing loss, neurological signs, cutaneous dyscromia and endocrinological problems seem to be potential predictors of pathological CNVs. Among patients carrying VOUS we analyzed genetic features including CNVs size, presence of deletion or duplication, genic density, multiple CNVs, to clinical features. Higher gene density was found in patients affected by ID. This result suggest that higher gene content has more chances to include pathogenic gene involved and causing ID in these patients.
CONCLUSION: Our study suggest the use of aCGH as first-tier test in patients with neurdevelopmental phenotypes. The inferred results have been used for building a flow-chart to be applied for children with ID.

PMID: 27072107 [PubMed - in process]

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1Na7Ti3
via IFTTT

Etiology and associated GJB2 mutations in Mauritanian children with non-syndromic hearing loss.

Related Articles

Etiology and associated GJB2 mutations in Mauritanian children with non-syndromic hearing loss.

Eur Arch Otorhinolaryngol. 2016 Apr 11;

Authors: Moctar EC, Riahi Z, El Hachmi H, Veten F, Meiloud G, Bonnet C, Abdelhak S, Errami M, Houmeida A

Abstract
Origins of all hearing impairment forms may be divided into genetic mutations and acquired influence. Both carry damage to the inner ear structure resulting in a mild to profound dysfunction of the auditory system. The purpose of this study was to assess the different etiologies of deafness in two reference centers for hearing-impaired children in Nouakchott/Mauritania. Data on gender, age, consanguinity, etiology and family history of deafness were gathered by interviewing the custodians of 139 children with hearing loss. DNA of pupils with hereditary non-syndromic deafness was then screened for GJB2 mutations by sequencing methods. Postnatal hearing loss was found in 36 (25.8 %) out of the 139 children surveyed. The main etiologies of this group were infections caused by meningitis (12.9 %) and measles (2.8 %). Unknown and ototoxic origins accounted for, respectively, 5.7 and 3.5 %. In 103 (74.1 %) children, deafness was identified near after the time of birth and, therefore, presumed as congenital. 56.8 % of deaf children had consanguineous parents. Two GJB2 mutations, c.del35G with an allele frequency of 4.7 % and R32C (3.7 %) were detected. Infections such as meningitis and measles were the most prevalent causes of postnatal deafness. In cases of congenital hearing impairment, two GJB2 allele variants, i.e., del35G and R32C (3.7 %) were detected. Extended genetic testing is recommended for a more comprehensive determination of congenital causes.

PMID: 27067584 [PubMed - as supplied by publisher]

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1Na7Ti1
via IFTTT

Mutations in PRPS1 causing syndromic or nonsyndromic hearing impairment: intrafamilial phenotypic variation complicates genetic counseling.

Related Articles

Mutations in PRPS1 causing syndromic or nonsyndromic hearing impairment: intrafamilial phenotypic variation complicates genetic counseling.

Pediatr Res. 2015 Jul;78(1):97-102

Authors: Gandía M, Fernández-Toral J, Solanellas J, Domínguez-Ruiz M, Gómez-Rosas E, Del Castillo FJ, Villamar M, Moreno-Pelayo MA, Del Castillo I

Abstract
BACKGROUND: PRPS1 encodes isoform I of phosphoribosylpyrophosphate synthetase (PRS-I), a key enzyme in nucleotide biosynthesis. Different missense mutations in PRPS1 cause a variety of disorders that include PRS-I superactivity, nonsyndromic sensorineural hearing impairment, Charcot-Marie-Tooth disease, and Arts syndrome. It has been proposed that each mutation would result in a specific phenotype, depending on its effects on the structure and function of the enzyme.
METHODS: Thirteen Spanish unrelated families segregating X-linked hearing impairment were screened for PRPS1 mutations by Sanger sequencing. In two positive pedigrees, segregation of mutations was studied, and clinical data from affected subjects were compared.
RESULTS: We report two novel missense mutations in PRPS1, p.Ile275Thr and p.Gly306Glu, which were found in the propositi of two unrelated Spanish families, both subjects presenting with nonsyndromic hearing impairment. Further investigation revealed syndromic features in other hemizygous carriers from one of the pedigrees. Sequencing of genes that are functionally related to PRPS1 did not reveal any candidate variant that might act as a phenotype modifier.
CONCLUSION: This case of intrafamilial phenotypic variation associated with a single PRPS1 mutation complicates the genotype-phenotype correlations, which makes genetic counseling of mutation carriers difficult because of the wide spectrum of severity of the associated disorders.

PMID: 25785835 [PubMed - indexed for MEDLINE]

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1Na7ThX
via IFTTT

Cochlear implantation in adolescents: Factors influencing compliance.

Related Articles

Cochlear implantation in adolescents: Factors influencing compliance.

Cochlear Implants Int. 2015 Jul;16(4):186-94

Authors: Markey AL, Nichani J, Lockley M, Melling C, Ramsden RT, Green KM, Bruce IA

Abstract
OBJECTIVES: To quantify rates of non- and partial-use of cochlear implants (CIs) in adolescent patients implanted in adolescence and childhood and identify factors influencing compliance.
METHODS: A retrospective case note review undertaken at The Manchester Auditory Implant Centre. Adolescents were defined as young people aged 11-18 years. Individuals implanted in adolescence were defined as Group 1, individuals implanted in childhood under the age of 3 years and currently adolescents were defined as Group 2 and individuals implanted between the age of 3 and11 years and currently adolescents were defined as Group 3. Non-use was defined as not using the CI at all and partial use was defined as consistently using the CI less than full-time, or fluctuating periods of full and less than full-time use.
RESULTS: In Group 1 there was 1 non-user (1.3%) and 11 partial-users (13.9%), with an overall non-compliance rate of 15.2%. In Group 2 there was one non-user (1.9%) and one partial-user (1.9%) with an overall non-compliance rate of 3.8%. In Group 3 there were no non-users and eight partial-users (9%), with an overall non-compliance rate of 9%. The factors influencing compliance differed between groups with the most common factor in Group 1 being a preference for the auditory input gained from the contralateral hearing aid (50%). In Groups 2 and 3 the main factors influencing compliance were behavioural and related to wearing the implant only at school (50 and 75%, respectively).
CONCLUSIONS: Patients implanted during adolescence have higher rates of non- and partial-use compared with their adolescent counterparts who have been implanted during childhood. It is important to investigate factors influencing non-compliance so appropriate support may be provided to the patient and their family.

PMID: 24624996 [PubMed - indexed for MEDLINE]

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1Q98vzb
via IFTTT

Sound Source Localization by Normal-Hearing Listeners, Hearing-Impaired Listeners and Cochlear Implant Listeners

Objective: Our primary aim was to determine whether listeners in the following patient groups achieve localization accuracy within the 95th percentile of accuracy shown by younger or older normal-hearing (NH) listeners: (1) hearing impaired with bilateral hearing aids, (2) bimodal cochlear implant (CI), (3) bilateral CI, (4) hearing preservation CI, (5) single-sided deaf CI and (6) combined bilateral CI and bilateral hearing preservation. Design: The listeners included 57 young NH listeners, 12 older NH listeners, 17 listeners fit with hearing aids, 8 bimodal CI listeners, 32 bilateral CI listeners, 8 hearing preservation CI listeners, 13 single-sided deaf CI listeners and 3 listeners with bilateral CIs and bilateral hearing preservation. Sound source localization was assessed in a sound-deadened room with 13 loudspeakers arrayed in a 180-degree arc. Results: The root mean square (rms) error for the NH listeners was 6 degrees. The 95th percentile was 11 degrees. Nine of 16 listeners with bilateral hearing aids achieved scores within the 95th percentile of normal. Only 1 of 64 CI patients achieved a score within that range. Bimodal CI listeners scored at a level near chance, as did the listeners with a single CI or a single NH ear. Listeners with (1) bilateral CIs, (2) hearing preservation CIs, (3) single-sided deaf CIs and (4) both bilateral CIs and bilateral hearing preservation, all showed rms error scores within a similar range (mean scores between 20 and 30 degrees of error). Conclusion: Modern CIs do not restore a normal level of sound source localization for CI listeners with access to sound information from two ears.
Audiol Neurotol 2016;21:127-131

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1S90E6Z
via IFTTT

The Short- and Long-Term Outcome of Intratympanic Steroid Therapy as a Salvage Treatment for Acute Low-Tone Sensorineural Hearing Loss without Episodes of Vertigo

Objectives: To evaluate the hearing outcomes of intratympanic steroid (ITS) treatment for patients with acute low-tone sensorineural hearing loss (ALHL) after failure of initial therapy and to investigate the recurrence and progression to definite Ménière's disease (MD) during a long-term follow-up. Methods: We retrospectively reviewed the medical records of 90 patients with refractory ALHL who were followed up for at least 1 year between January 2000 and April 2014. Patients who responded poorly to initial medical treatment received intratympanic dexamethasone injections (ITS group) or isosorbide administration for 4 weeks (diuretic group) as salvage treatment options according to their choice of management. The control group did not receive ITS or the diuretic, due to their refusal of both medical treatments. The hearing outcomes were evaluated 1 month, 1 year and 5 years after the completion of the second-line therapy, and the rates of recurrence and progression to MD were measured during a follow-up period of at least 1 year. Results: Twenty-seven patients in the ITS group, 39 patients in the diuretic group and 24 patients in the control group were enrolled. Of these, 12 patients in the ITS group, 15 patients in the diuretic group and 12 patients in the control group were followed up for over 5 years. We found that the recovery rates and the audiometric functional values after 1 month and 1 year in the ITS group were significantly higher than those in the diuretic and control groups. However, there were no significant differences in the recovery rates or the audiometric functional values after 5 years, or in the rates of recurrence and progression to MD between the groups. Conclusions: Salvage ITS therapy can provide a relatively good short-term hearing outcome for ALHL patients who have persistent hearing loss despite conventional treatment. However, both recurrence and progression to MD after treatment were observed in some patients during the long-term follow-up.
Audiol Neurotol 2016;21:132-140

from #Audiology via xlomafota13 on Inoreader http://ift.tt/1VY2xbe
via IFTTT