美国辛辛那提大学的科研人员日前发现了一个导致耳聋的新致病基因。这一研究成果将帮助科研人员研制新的药物,治疗罹患这一综合征的患者。
论文主要作者、辛辛那提大学研究人员祖拜尔·艾哈迈德博士说,“研究人员通过基因分析,精确地找到了尤塞氏综合征1型耳聋和非综合征耳聋的致病基因,它的名字叫CIB2蛋白。”
尤塞氏综合征是一种因基因缺陷而导致耳聋,及由视网膜色素变性引起的视觉逐步减退的疾病。尤塞氏综合征1型患者在出生时便严重失聪,随之而来的是身体平衡出现问题,到成年后开始出现夜盲和丧失周边视觉的症状。
相关研究论文已刊登在新一期《自然遗传学》杂志网络版上。(生物谷Bioon.com)
doi:10.1038/ng.2426
PMC:
PMID:
Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48
Riazuddin S, Belyantseva IA, Giese AP, Lee K, Indzhykulian AA, Nandamuri SP, Yousaf R, Sinha GP, Lee S, Terrell D, Hegde RS, Ali RA, Anwar S, Andrade-Elizondo PB, Sirmaci A, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Ahmad W, Khan SN, Akram J, Tekin M, Riazuddin S, Cook T, Buschbeck EK, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZM.
Sensorineural hearing loss is genetically heterogeneous. Here, we report that mutations in CIB2, which encodes a calcium- and integrin-binding protein, are associated with nonsyndromic deafness (DFNB48) and Usher syndrome type 1J (USH1J). One mutation in CIB2 is a prevalent cause of deafness DFNB48 in Pakistan; other CIB2 mutations contribute to deafness elsewhere in the world. In mice, CIB2 is localized to the mechanosensory stereocilia of inner ear hair cells and to retinal photoreceptor and pigmented epithelium cells. Consistent with molecular modeling predictions of calcium binding, CIB2 significantly decreased the ATP-induced calcium responses in heterologous cells, whereas mutations in deafness DFNB48 altered CIB2 effects on calcium responses. Furthermore, in zebrafish and Drosophila melanogaster, CIB2 is essential for the function and proper development of hair cells and retinal photoreceptor cells. We also show that CIB2 is a new member of the vertebrate Usher interactome.