Human Disease Model Report: neuronopathy, distal hereditary motor, autosomal dominant 8

General Information

Name

neuronopathy, distal hereditary motor, autosomal dominant 8

FlyBase ID

FBhh0001242

Disease Ontology Term

autosomal dominant distal hereditary motor neuronopathy 8

Parent Disease

neuronopathy, distal hereditary motor, autosomal dominant

OMIM

NEURONOPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL DOMINANT 8; HMND8

Overview

Neuronopathy, distal hereditary motor, autosomal dominant 8 (HMND8) is one of several neuromuscular disorders associated with the human TRPV4 gene. See the human disease model report for neuromuscular diseases, TRPV4-related (FBhh0001240) for information on experimental results using Drosophila models of this and related diseases.

UAS constructs of the human Hsap\TRPV4 gene have been introduced into flies, including wild-type and variants implicated in disease. See the 'Disease-Implicated Variants' table below.

[updated Feb. 2024 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: neuronopathy, distal hereditary motor, autosomal dominant

Symptoms and phenotype

Distal hereditary motor neuronopathy (dHMN or HMN) is a heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration and characterized by progressive distal motor weakness and muscular atrophy of the peripheral nervous system without sensory impairment. Distal HMN is also referred to as spinal Charcot-Marie-Tooth disease (spinal CMT). Distal HMN is often referred to as a 'neuronopathy' instead of a 'neuropathy' based on the hypothesis that the primary pathologic process resides in the neuron cell body and not in the axons (Irobi et al., 2006, pubmed:16775372). [From MIM:607641, 2016.01.11]

(OMIM, 2013-)

Specific Disease Summary: neuronopathy, distal hereditary motor, autosomal dominant 8

OMIM report

[NEURONOPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL DOMINANT 8; HMND8](https://omim.org/entry/600175)

Human gene(s) implicated

[TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY V, MEMBER 4; TRPV4](https://omim.org/entry/605427)

Symptoms and phenotype

A nonprogressive congenital lower motor neuron disorder usually restricted to the lower part of the body. Variable expression is observed within a single family. [from MIM:600175; 2020.08.16]

(OMIM, 2013-)

Genetics

Autosomal dominant distal hereditary motor neuronopathy-8 (HMND8) is caused by heterozygous mutation in the TRPV4 gene. [from MIM:600175; 2024.02.20]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

External links

Gene2Function (human gene): TRPV4
Gene Cards: TRPV4
MedlinePlus (gene): TRPV4
MARRVEL (human gene): TRPV4
NCBI MedGen: Distal spinal muscular atrophy, congenital nonprogressive (HMN8)
NCBI (Entrez) gene: TRPV4; transient receptor potential cation channel subfamily V member 4

Disease synonyms

DHMN8

HMN8

neuronopathy, distal hereditary motor, autosomal dominant 8

neuronopathy, distal hereditary motor, type VIII

neuropathy, distal hereditary motor, type VIII

spinal muscular atrophy, congenital, benign, with contractures

spinal muscular atrophy, distal, congenital nonprogressive

Related Diseases

Related human health report(s)

neuromuscular diseases, TRPV4-related

Related Specific Diseases

OMIM phenotypic series

Neuronopathy, distal hereditary motor, autosomal dominant

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[HMND1](https://omim.org/entry/182960)

[HMND2](https://omim.org/entry/158590)

[HSPB8](https://omim.org/entry/608014)

neuronopathy, distal hereditary motor, autosomal dominant 2

[HMND3](https://omim.org/entry/608634)

[HSPB1](https://omim.org/entry/602195)

neuronopathy, distal hereditary motor, autosomal dominant 3

[HMND4](https://omim.org/entry/613376)

[HSPB3](https://omim.org/entry/604624)

neuronopathy, distal hereditary motor, autosomal dominant 4

[HMND5](https://omim.org/entry/600794)

[GARS1](https://omim.org/entry/600287)

neuronopathy, distal hereditary motor, autosomal dominant 5

[HMND6](https://omim.org/entry/615575)

[FBXO38](https://omim.org/entry/608533)

[HMND7](https://omim.org/entry/158580)

[SLC5A7](https://omim.org/entry/608761)

[HMND8](https://omim.org/entry/600175)

[TRPV4](https://omim.org/entry/605427)

neuronopathy, distal hereditary motor, autosomal dominant 8

[HMND9](https://omim.org/entry/617721)

[WARS1](https://omim.org/entry/191050)

[HMND10](https://omim.org/entry/620080)

[EMILIN1](https://omim.org/entry/130660)

[HMND11](https://omim.org/entry/620528)

[SPTAN1](https://omim.org/entry/182810)

[HMND13](https://omim.org/entry/619112)

[BSCL2](https://omim.org/entry/606158)

[HMND14](https://omim.org/entry/607641)

[DCTN1](https://omim.org/entry/601143)

neuronopathy, distal hereditary motor, autosomal dominant 14

Ortholog Information

Human gene(s) in FlyBase

Hsap\TRPV4

Human gene (HGNC)

Symbol / Name

TRPV4; transient receptor potential cation channel subfamily V member 4

D. melanogaster ortholog (based on DIOPT)

Dmel\nan

(DIOPT, 2013-)

Dmel\iav

(DIOPT, 2013-)

Comments on ortholog(s)

Many to many: multiple related genes in both species.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (0)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (0 groups)

Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)

Hsap\TRPV4

Models Based on Experimental Evidence ( 5 )

Allele

Disease

Evidence

References

Hsap\TRPV4^UAS.cWa

model of neuromuscular disease

CEA

(Woolums et al., 2020)

Hsap\TRPV4^R269C.UAS

model of neuromuscular disease

CEA

(Woolums et al., 2020)

model of neuropathy

CEA

(McCray et al., 2021)

Hsap\TRPV4^{R269C.M680K.UAS}

DOES NOT model neuromuscular disease

CEA

(Woolums et al., 2020)

Hsap\TRPV4^R232C.UAS

model of neuromuscular disease

CEA

(Woolums et al., 2020)

Hsap\TRPV4^{R269C.UAS.BID}

model of neuromuscular disease

CEA with CaMKII^UAS.cKa

(Woolums et al., 2020)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Hsap\TRPV4^UAS.cWa

model of neuromuscular disease

is ameliorated by CaMKII^RNAi.UAS.cUa

(Woolums et al., 2020)

is ameliorated by CaMKII^GD9506

(Woolums et al., 2020)

is ameliorated by CaMKII^KK107335

(Woolums et al., 2020)

Hsap\TRPV4^R269C.UAS

model of neuromuscular disease

is ameliorated by CaMKII^GD9506

(Woolums et al., 2020)

is ameliorated by CaMKII^KK107335

(Woolums et al., 2020)

is ameliorated by CaMKII^RNAi.UAS.cUa

(Woolums et al., 2020)

model of neuropathy

is ameliorated by Rho1^N19.UAS

(McCray et al., 2021)

Hsap\TRPV4^{R269C.UAS.BID}

model of neuromuscular disease

is exacerbated by Miro^{A20V.UAS.Tag:MYC}

(Woolums et al., 2020)

is exacerbated by Miro^UAS.cGa

(Woolums et al., 2020)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Hsap\TRPV4^{R269C.M680K.UAS}

P{UAS-hTRPV4.R269C.M680K}

Hsap\TRPV4^R232C.UAS

P{UAS-hTRPV4.R232C}

Hsap\TRPV4^{R269C.UAS.BID}

P{UAS-hTRPV4.R269C.BID}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

References (4)

Report Sections

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