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Abstract: Pendred syndrome (PS) is an autosomal recessive disorder characterized by congenital bilateral sensorineural hearing loss, goiter, and incomplete iodide organification. Patients with PS also have structural anomalies of the inner ear such as enlarged vestibular aqueducts (EVA) and Mondini''s malformation. The goiter, which is a major clinical manifestation of PS, usually develops around adolescence. PS is caused by biallelic mutations of the SLC26A4 gene, while nonsyndromic bilateral EVA is associated with zero or one SLC26A4 mutant allele. We report here a Korean family including a young female with PS who had goiter and progressive, fluctuating sensorineural hearing loss that could be partially recovered by oral steroid treatment. Genetic investigation revealed compound heterozygous mutations for p.R677AfsX11, a novel frameshift mutation, and p.H723R in the SLC26A4 gene. Our findings provide detailed information regarding the distribution of mutant alleles for PS and may serve as a foundation for studies to comprehend the genetic portion of syndromic hearing loss. [Copyright &y& Elsevier]

Hereditary hearing loss (HHL) is a common genetically heterogeneous disorder, which follows Mendelian inheritance in humans. Because of this heterogeneity, the identification of the causative gene of HHL by linkage analysis or Sanger sequencing have shown economic and temporal limitations. With recent advances in next-generation sequencing (NGS) techniques, rapid identification of a causative gene via massively parallel sequencing is now possible. We recruited a Korean family with three generations exhibiting autosomal dominant inheritance of hearing loss (HL), and the clinical information about this family revealed that there are no other symptoms accompanied with HL. To identify a causative mutation of HL in this family, we performed whole-exome sequencing of 4 family members, 3 affected and an unaffected. As the result, A novel splicing mutation, c.763 + 1G > T, in the solute carrier family 17, member 8 ( SLC17A8 ) gene was identified in the patients, and the genotypes of the mutation were co-segregated with the phenotype of HL. Additionally, this mutation was not detected in 100 Koreans with normal hearing. Via NGS, we detected a novel splicing mutation that might influence the hearing ability within the patients with autosomal dominant non-syndromic HL. Our data suggests that this technique is a powerful tool to discover causative genetic factors of HL and facilitate diagnoses of the primary cause of HHL. [ABSTRACT FROM AUTHOR]

Abstract: Auditory neuropathy spectrum disorder (ANSD) is caused by dys-synchronous auditory neural response as a result of impairment of the functions of the auditory nerve or inner hair cells, or synapses between inner hair cells and the auditory nerve. To identify a causative gene causing ANSD in the Korean population, we conducted gene screening of the OTOF, DIAPH3, and PJVK genes in 19 unrelated Korean patients with ANSD. A novel nonsense mutation (p.Y1064X) and a known pathogenic mutation (p.R1939Q) of the OTOF gene were identified in a patient as compound heterozygote. Pedigree analysis for these mutations showed co-segregation of mutation genotype and the disease in the family, and it supported that the p.Y1064X might be a novel genetic cause of autosomal recessive ANSD. A novel missense variant p.K1017R (c.3050A>G) in the DIAPH3 gene was also identified in the heterozygous state. In contrast, no mutation was detected in the PJVK gene. These results indicate that no major causative gene has been reported to date in the Korean population and that pathogenic mutations in undiscovered candidate genes may have an effect on ANSD. [Copyright &y& Elsevier]