Communication outcomes following cochlear implantation in a child with cystic cochleovestibular anomaly

Cochlear implantation is one of the best amongst the various management options available for children and adults with severe to profound sensorineural hearing loss.Inner ear and internal auditory canal(IAC) malformations accounts to approximately 25% of congenital sensorineural hearing loss in children.The primary goal of this report was to evaluate the communication outcomes after cochlear implantation in a child with cystic cochleovestibular anomaly(CCVA).The child was evaluated through various standardized outcome measures at regular intervals to track the progress in terms of auditory and spoken language skills.The scores on Categories of Auditory Perception(CAP),Meaningful Auditory Integration Scale(MAIS),Speech Intelligibility Rating(SIR),Meaningful Use of Speech Scale(MUSS),and listening and spoken language skills showed a significant leap in 12 months duration post implantation.The report thus highlights and correlates the significant progress in auditory and spoken language skills of the child with congenital malformations to appropriate auditory rehabilitation and intensive parental training.

Phosphatidylinositol 4-kinase β mutations cause nonsyndromic sensorineural deafness and inner ear malformation

Congenital hearing loss is a common disorder worldwide.Heterogeneous gene variation accounts for approximately 20-25%of such patients.We investigated a five-generation Chinese family with autosomaldominant nonsyndromic sensorineural hearing loss(SNHL).No wave was detected in the pure-tone audiometry,and the auditory brainstem response was absent in all patients.Computed tomography of the patients,as well as of two sporadic SNHL cases,showed bilateral inner ear anomaly,cochlear maldevelopment,absence of the osseous spiral lamina,and an enlarged vestibular aqueduct.Such findings were absent in nonaffected persons.We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4 KB gene(p.Gln121 Arg)encoding phosphatidylinositol 4-kinaseβ(PI4 KB)from the patients in this family.In addition,3 missense PI4 KB(p.Val434 Gly,p.Glu667 Lys,and p.Met739 Arg)mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases.No such mutations were present within 600 Chinese controls,the 1000 genome project,gnom AD,or similar databases.Depleting pi4 kb m RNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment,mimicking the patient phenotypes.Moreover,overexpression of 4 human missense PI4 KB mutant m RNAs in zebrafish embryos resulted in impaired hearing function,suggesting dominant-negative effects.Taken together,our results reveal that PI4 KB mutations can cause SNHL and inner ear malformation.PI4 KB should be included in neonatal deafness screening.

Phenotypic similarities in pigs with SOX10^(c.321dupC)and SOX10^(c.325A>T)mutations implied the correlation of SOX10 haploinsufficiency with Waardenburg syndrome

SOX10 is a causative gene of Waardenburg syndrome(WS)that is a rare genetic disorder characterized by hearing loss and pigment disturbance.More than 100 mutations of SOX10 have been found in patients with Type 2 WS(WS2),Type 4 WS(WS4),and more complex syndromes.However,no mutation hotspot has been detected in SOX10,and most cases are sporadic,making it difficult to establish a correlation between the high phenotypic and genetic variability.In this study,a duplication of the 321th cytosine(c.321dupC)was introduced into SOX10 in pigs,which induced premature termination of the translation of SOX10(p.K108QfsX45).The premature stop codon in Exon 3 triggered the degradation of mutant mRNA through nonsense-mediated mRNA decay.However,SOX10^(c.321dupC) induced a highly similar phenotype of WS2 with heterogeneous inner ear malformation compared with its adjacent missense mutation SOX10^(c.325A>T).In addition,a site-saturation mutation analysis of the SOX10 N-terminal nuclear localization signal(n-NLS),where these two mutations located,revealed the correlation between SOX10 haploinsufficiency and WS by an in vitro reporter assay.The analysis combining the in vitro assay with clinical cases may provide a clue to clinical diagnoses.