Weil D, Levy G, Sahly I, Levi-Acobas F, Blanchard S, El-Amraoui A, Crozet F, Philippe H, Abitbol M, Petit C
Unite de Genetique Moleculaire Humaine, Centre National de la Recherche Scientifique Unite de Recherche Associee 1968, Institut Pasteur, Paris, France.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3232-7. doi: 10.1073/pnas.93.8.3232.
The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.
编码人类肌球蛋白VIIA的基因与III型遗传性耳聋综合征（USH1B）相关，该疾病伴有严重的先天性感音神经性耳聋、前庭功能障碍和色素性视网膜炎。本文给出的重组cDNA序列预测该蛋白有2215个氨基酸，具有典型的非常规肌球蛋白结构。预计该蛋白会二聚化形成双头分子。其尾部的C末端与4.1带蛋白超家族的膜结合结构域具有同源性。该基因由48个编码外显子组成。它编码几种可变剪接形式。对人类胚胎进行的原位杂交分析表明，肌球蛋白VIIA基因在视网膜的色素上皮和光感受器细胞中表达，因此表明这两种细胞类型可能都参与了USH1B视网膜变性过程。此外，该基因在人类胚胎耳蜗和前庭神经上皮中表达。我们认为，USH1B患者的耳聋和前庭功能障碍是由于内耳感觉细胞静纤毛形态发生缺陷所致。
