Human Disease Model Report: myopathy, areflexia, respiratory distress, and dysphagia, early-onset

General Information

Name

myopathy, areflexia, respiratory distress, and dysphagia, early-onset

FlyBase ID

FBhh0000393

Disease Ontology Term

early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome

Parent Disease

OMIM

CONGENITAL MYOPATHY 10A, SEVERE VARIANT; CMYO10A

Overview

This report describes myopathy, areflexia, respiratory distress, and dysphagia, early-onset (EMARDD), an autosomal recessive form of congenital myopathy. The human gene implicated in this disease is MEGF10, which encodes a protein that contains multiple EGF-like domains and plays a role in cell adhesion, motility and proliferation, apoptotic cell phagocytosis, and amyloid-beta peptide uptake in the brain. There is a single fly ortholog, drpr, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\drpr is also orthologous to three other genes in human, MEGF11, PEAR1, and MEGF6.

The human MEGF10 gene has not been introduced into flies.

Animals homozygous for an amorphic mutation of Dmel\drpr survive to adulthood, but show an age-dependent decline in locomotor activity. In larval, pupal, and adult stages, defects in phagocytic clearance of debris in neurons are observed following injury or normal dendritic pruning. Physical and genetic interactions have been described for drpr; see below and in the gene report for drpr.

[updated Sep. 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: myopathy, areflexia, respiratory distress, and dysphagia, early-onset

OMIM report

[CONGENITAL MYOPATHY 10A, SEVERE VARIANT; CMYO10A](https://omim.org/entry/614399)

Human gene(s) implicated

[MULTIPLE EPIDERMAL GROWTH FACTOR-LIKE DOMAINS 10; MEGF10](https://omim.org/entry/612453)

Symptoms and phenotype

This disorder represents a congenital myopathy characterized by proximal and generalized muscle weakness, respiratory difficulties, joint contractures, and scoliosis. [from MIM:614399; 2016.09.08]

(OMIM, 2013-)

Genetics

EMARDD, a form of congenital myopathy, is caused by homozygous or compound heterozygous mutation in the MEGF10 gene (autosomal recessive). [from MIM:614399; 2016.09.08]

(OMIM, 2013-)

Cellular phenotype and pathology

Muscle biopsies from affected individuals show myopathic changes, replacement of myofibers with fatty tissue, small and incompletely fused muscle fibers, and variation in fiber size. Short regions of sarcomeric disorganization with few or no mitochondria (minicores) have been observed in some cases. [from UniProt:Q96KG7; 2016.09.08]

(FlyBase Curators, 2013-)

Molecular information

The multiple EGF-like domains 10 gene (MEGF10) encodes a protein that plays a role in cell adhesion, motility and proliferation; is a critical mediator of apoptotic cell phagocytosis and amyloid-beta peptide uptake in the brain. [Genetics Home Reference, MEGF10; 2016.09.08]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): MEGF10
Gene Cards: MEGF10
MedlinePlus (gene): MEGF10
MARRVEL (human gene): MEGF10
NCBI MedGen: Myopathy, areflexia, respiratory distress, and dysphagia, early-onset (EMARDD)
NCBI (Entrez) gene: MEGF10; multiple EGF like domains 10

Disease synonyms

early-onset myopathy, areflexia, respiratory distress, and dysphagia

EMARDD

Related Diseases

Related human health report(s)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

MEGF10; multiple EGF like domains 10

D. melanogaster ortholog (based on DIOPT)

Dmel\drpr

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 4 human to 1 Drosophila. The additional human genes are MEGF11, PEAR1, and MEGF6.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\drpr

Gene Snapshot

draper (drpr) encodes a single-pass transmembrane receptor that is involved in phagocytosis by glia, macrophages, and epithelia. It signals downstream through the proteins encoded by Src42A and Shark to promote Rac1 function and transcriptional changes through the products of Jra and Stat92E. It is also required for activation of autophagy in salivary glands. [Date last reviewed: 2019-03-21]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

NIMR

Comments on ortholog(s)

One to many: Dmel\drpr is a high-scoring ortholog of human MEGF10 and MEGF11; lower-scoring ortholog of PEAR1 and MEGF6. Dmel\drpr shares 34-35% identity and 47% similarity with MEGF10 and MEGF11.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

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

Summary of Physical Interactions (9 groups)

drpr

protein-protein

Interacting group

Assay

References

drpr - CaBP1

solid phase assay, identification by antibody, affinity chromatography technology, Identification by mass spectrometry

(Okada et al., 2012)

drpr - ced-6

pull down, western blot

(Awasaki et al., 2006)

drpr - csw

anti bait coimmunoprecipitation, anti tag western blot

(Logan et al., 2012)

drpr - ctg

anti tag coimmunoprecipitation, anti tag western blot

(Sung et al., 2024)

drpr - galectin

anti tag coimmunoprecipitation, anti tag western blot

(Sung et al., 2024)

drpr - orion

colocalization, fluorescence microscopy, inferred by author

(Ji et al., 2023)

drpr - prtp

pull down, peptide massfingerprinting, anti tag western blot, western blot

(Fujita et al., 2012, Kuraishi et al., 2009)

drpr - Shark

two hybrid, fluorescent resonance energy transfer, fluorescence technology, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation

(Williamson and Vale, 2018, Lu et al., 2017, Logan et al., 2012, Ziegenfuss et al., 2008)

drpr - Traf4

anti tag coimmunoprecipitation, anti tag western blot

(Lu et al., 2017)

Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)

drpr

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

drpr^Δ5