更新于：2024-11-01

Neuropathy, Distal Hereditary Motor, Type VIIA

远端遗传性运动神经元病 VIIA型

更新于：2024-11-01

基本信息

别名

DHMN7A、DHMNVP、HARPER-YOUNG MYOPATHY

+ [13]

简介-

关联

项与远端遗传性运动神经元病 VIIA型相关的药物

Recombinant human coagulation factor VIIa(Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd.)

重组人凝血因子Ⅶa (南京正大天晴制药)

靶点

tissue factor

作用机制

tissue factor抑制剂

在研机构

正大天晴药业集团南京顺欣制药有限公司 [+1]

原研机构

南京正大天晴制药有限公司

在研适应症

血友病A [+3]

非在研适应症

远端遗传性运动神经元病 VIIA型

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期1800-01-20

项与远端遗传性运动神经元病 VIIA型相关的临床试验

CTR20202311 / Completed临床1期

注射用重组人凝血因子VIIa在伴有抑制物血友病患者中的药代及药效学（PK/PD）试验

评价注射用重组人凝血因子VIIa 在伴有抑制物血友病患者中的PK/PD 特征。

开始日期2020-12-15

申办/合作机构

正大天晴药业集团股份有限公司

[+1]

100 项与远端遗传性运动神经元病 VIIA型相关的临床结果

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100 项与远端遗传性运动神经元病 VIIA型相关的转化医学

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0 项与远端遗传性运动神经元病 VIIA型相关的专利（医药）

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项与远端遗传性运动神经元病 VIIA型相关的文献（医药）

2018-01-01·Journal of Biological Chemistry2区 · 生物学

The shaker-1 mouse myosin VIIa deafness mutation results in a severely reduced rate of the ATP hydrolysis step

2区 · 生物学

Article

作者: McConnell, Matthew ; Liu, Yingying ; Forgacs, Eva ; Belknap, Betty ; Eusner, Lauren ; White, Howard D ; Haithcock, Jessica ; Xiong, Ailian

Mutations in the MYO7A gene, encoding the motor protein myosin VIIa, can cause Usher 1B, a deafness/blindness syndrome in humans, and the shaker-1 phenotype, characterized by deafness, head tossing, and circling behavior, in mice. Myosin VIIa is responsible for tension bearing and the transduction mechanism in the stereocilia and for melanosome transport in the retina, in line with the phenotypic outcomes observed in mice. However, the effect of the shaker-1 mutation, a R502P amino acid substitution, on the motor function is unclear. To explore this question, we determined the kinetic properties and the effect on the filopodial tip localization of the recombinant mouse myosin VIIa-5IQ-SAH R502P (myoVIIa-sh1) construct. Interestingly, although residue 502 is localized to a region thought to be involved in interacting with actin, the kinetic parameters for actin binding changed only slightly for the mutant construct. However, the rate constant for ATP hydrolysis (k_+H + k_-H) was reduced by ∼200-fold from 12 s^-1 to 0.05 s^-1, making the hydrolysis step the rate-limiting step of the ATPase cycle in the presence and absence of actin. Given that wild-type mouse myosin VIIa is a slow, high-duty ratio, monomeric motor, this altered hydrolysis rate would reduce activity to extremely low levels. Indeed, the translocation to the filopodial tips was hampered by the diminished motor function of a dimeric construct of the shaker-1 mutant. We conclude that the diminished motor activity of this mutant is most likely responsible for impaired hearing in the shaker-1 mice.

2000-08-01·Journal of Medical Genetics

Distal spinal muscular atrophy with vocal cord paralysis (dSMA-VII) is not linked to the MPD2 locus on chromosome 5q31

Letter

作者: Jackson, C ; Harper, P ; Spurlock, G ; Rahman, N ; McEntagart, M

Editor—Hereditary distal limb weakness and atrophy is a heterogeneous condition that may be neurogenic or myopathic in origin. Hereditary motor and sensory neuropathy (HMSN) I and II (also known as Charcot-Marie-Tooth (CMT) 1 and 2), distal spinal muscular atrophy (dSMA), and the distal myopathies may all present with this clinical picture. Traditionally, these disorders were differentiated according to electrophysiological and histopathological characteristics, with subtypes of each group identified on the basis of inheritance pattern, age of onset, and associated clinical features. The localisation of several genes that confer susceptibility to these disorders has necessitated the re-evaluation of current classification systems, as conditions that were clinically classified as distinct are now known to be allelic at the genetic level. Vocal cord weakness/paralysis is occasionally associated with distal muscular atrophy. This association was first described by Young and Harper1 in a Welsh family in which the disorder segregated in an autosomal dominant fashion. The presentation was one of progressive distal muscle wasting and weakness together with a dysphonic or hoarse voice. Motor and sensory nerve conduction was normal with the exception of one patient who showed mild motor slowing. Spontaneous fibrillation was detected on EMG. Unilateral or bilateral vocal cord palsy was present in all affected subjects. The findings were consistent with anterior horn cell disease and the condition was assumed to be a form of dSMA associated with vocal cord paralysis. In a subsequent classification of the proximal and distal spinal muscular atrophies the disorder was designated dSMA type VII.2 Recently, a family with vocal cord and pharyngeal weakness associated with a distal myopathy was reported.3 This family has …

1997-06-01·Genes and Function

Mutation analysis of the mouse myosin VIIA deafness gene

Article

作者: Brown, Steve ; Walsh, James ; Kendrick‐Jones, John ; Steel, Karen ; Liu, Xue Zhong ; Saw, Dennis ; Gibson, Fernando ; Mburu, Philomena ; Cope, M.

The shaker‐1 (Myo7a) mouse deafness locus is encoded by an unconventional myosin gene: myosin VIIA [Gibson, Walsh, Mburu, Varela, Brown, Antonio, Biesel, Steel and Brown (1995) Nature (London) 374, 62–64]. The myosin VIIA gene is expressed in hair cells in the cochlea, where it is thought to function in the development of the critical neuroepithelium where auditory transduction takes place. In order to understand better the function of myosin VIIA, we have determined the complete sequence of the mouse myosin VIIA cDNA and employed the wild‐type sequence for mutational analysis of a number of shaker‐1 alleles. Analysis of the mouse myosin VIIA tail sequence demonstrates a large internal repeat with regions of similarity to myosins IV, X and XII as well as members of the band 4.1 family. In addition, the myosin VIIA repeats are similar along their entire length to a tail domain from a plant kinesin. The mouse myosin VIIA tail also contains a putative Src homology 3 (SH3) domain. Along with three previously reported shaker‐1 mutations, mutations for seven shaker‐1 alleles in total have now been identified. The mutational changes have been analysed in terms of their predicted effect on both myosin motor head and tail domain function and the predictions related to the known phenotypes of the shaker‐1 alleles. Five of the mutations lie in the motor head, and analysis of their likely effect on myosin head structure correlates well with the known severity of the shaker‐1 alleles. Of the two mutations in the tail, one is a missense mutation within the kinesin and myosin IV, X and XII homology domains that substitutes a conserved amino acid and leads to a severe deafness phenotype. This and other data suggest that myosin VIIA may have properties of a myosin‐motor–kinesin‐tail hybrid and be involved in membrane turnover within the actin‐rich environment of the apical hair cell surface.