一项研究说，科学家发现了一种基因突变可能导致一种称为听觉神经病的罕见听觉丧失，而且有可能带来这种疾病的一种遗传测试。 听觉神经病是一种外耳功能正常、但是到达内耳的声音不能正确地传递给大脑的疾病。Marci Lesperance及其同事检查了来自同一个大家族的受该病影响的人的DNA，结果发现了一种突变可能导致了DIAPH3基因过度制造一种称为透明蛋白质的化合物。此前的研究已经把听力丧失与也调控着一种透明蛋白质的一种相关基因联系了起来。为了调查这些化合物在听觉功能中的作用，这组作者改造了一个果蝇品系，让它们在听觉器官中表达出了透明蛋白的类似物。利用声音诱导产生了可测量的电压变化，这组科学家确定了被测果蝇的听力比野生型对照组果蝇显著衰退。目前，诊断听觉神经病需要测试专门证实只有外耳的功能正常。这组作者说，一种遗传测试可能导致更少的误诊。
论文 #10-03027: "Increased activity of Diaphanous homolog 3 (DIAPH3)/diaphanous causes hearing defects in humans with auditory neuropathy and in Drosophila," 作者 Cynthia J. Schoen, Sarah B. Emery, Marc C. Thorne, Hima R. Ammana, Elzbieta Sliwerska, Jameson Arnett, Michael Hortsch, Frances Hannan, Margit Burmeister和Marci M. Lesperance
媒体联系人：Marci Lesperance，密歇根大学耳鼻喉学系
Department of Otolaryngology, University of Michigan, Ann Arbor, MI
电话：734-936-9816
电子邮件：lesperan@umich.edu
Published online before print July 12, 2010, doi: 10.1073/pnas.1003027107
Increased activity of Diaphanous homolog 3 (DIAPH3)/diaphanous causes hearing defects in humans with auditory neuropathy and in Drosophila
Cynthia J. Schoena,b, Sarah B. Emeryc, Marc C. Thornec, Hima R. Ammanad, El|bieta Zliwerskab, Jameson Arnettc, Michael Hortsche, Frances Hannand,f, Margit Burmeisterb,g,h, and Marci M. Lesperancec,1
Abstract
Auditory neuropathy is a rare form of deafness characterized by an absent or abnormal auditory brainstem response with preservation of outer hair cell function. We have identified Diaphanous homolog 3 (DIAPH3) as the gene responsible for autosomal dominant nonsyndromic auditory neuropathy (AUNA1), which we previously mapped to chromosome 13q21-q24. Genotyping of additional family members narrowed the interval to an 11-Mb, 3.28-cM gene-poor region containing only four genes, including DIAPH3. DNA sequencing of DIAPH3 revealed a c.-172G < A, g. 48G < A mutation in a highly conserved region of the 5′ UTR. The c.-172G < A mutation occurs within a GC box sequence element and was not found in 379 controls. Using genome-wide expression arrays and quantitative RT-PCR, we demonstrate a 2- to 3-fold overexpression of DIAPH3 mRNA in lymphoblastoid cell lines from affected individuals. Likewise, a significant increase (≈1.5-fold) in DIAPH3 protein was found by quantitative immunoblotting of lysates from lymphoblastoid cell lines derived from affected individuals in comparison with controls. In addition, the c.-172G < A mutation is sufficient to drive overexpression of a luciferase reporter. Finally, the expression of a constitutively active form of diaphanous protein in the auditory organ of Drosophila melanogaster recapitulates the phenotype of impaired response to sound. To date, only two genes, the otoferlin gene OTOF and the pejvakin gene PJVK, are known to underlie nonsyndromic auditory neuropathy. Genetic testing for DIAPH3 may be useful for individuals with recessive as well as dominant inheritance of nonsyndromic auditory neuropathy.
