OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.
Asian Continental Ancestry Group ; Child ; Clinical Coding ; Computer Simulation ; Deafness ; Exons ; Extravehicular Activity ; Frameshift Mutation ; Hearing Loss ; Heterozygote ; Humans ; Introns ; Mass Screening ; Parents ; Sequence Homology ; Siblings ; Vestibular Aqueduct

Objective: To study the difference expression and diagnostic value of ribosomal protein L5 (RPL5) in papillary thyroid carcinoma (PTC) of children and adults. Methods: Realtime-PCR was performed to detect the expression of RPL5 in 22 PTC tissues and 13 pericarcinous tissues. Receiver operating characteristic (ROC) curve and Youden's index were used to evaluate the diagnostic value of RPL5 in PTC of children and adults. Results: The expression of RPL5 in PTC tissues was higher than in pericarcinous tissues. The area under curve (AUC) was 0.820 (P=0.001), and Youden′s index was 0.568. The expression of RPL5 in PTC of adults was higher than children (P<0.05). The AUC and Youden's index were respectively 0.721 (P=0.069) and 0.414 in children, whereas being respectively 0.896 (P=0.0005) and 0.709 in adults. RPL5 in diagnosis of PTC of adults was better than CK19, Galectin-3 and TPO, which are commonly used for the pathologic diagnosis of PTC. Conclusion The expression of RPL5 in PTC is higher than pericarcinous tissues, and its expression in PTC of adults is higher than children. Furthermore, PTC is a potential indicator for diagnosis of PTC.