This report describes cerebellar atrophy, visual impairment, and psychomotor retardation (CAVIPMR). The human gene implicated in this disease is EMC1, which encodes a subunit of the ER membrane protein complex. There is a single orthologous gene in Drosophila, Dmel\EMC1, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the wild-type human Hsap\EMC1 gene have been introduced into flies. Partial heterologous rescue (functional complementation) is observed for glial-specific RNAi knockdown phenotypes of Dmel\EMC1.
Variants implicated in CAVIPMR have been introduced into flies as UAS constructs of the Dmel\EMC1 gene. See the 'Disease-Implicated Variants' table below. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): P506H in the fly EMC1 gene [corresponds to P582H in the human EMC1 gene]; P506R in the fly EMC1 gene [corresponds to P582R in the human EMC1 gene]; P509H in the fly EMC1 gene [corresponds to P584H in the human EMC gene]. Ubiquitous overexpression of these variants is less lethal than overexpression of wild-type Dmel\EMC1. Ubiquitous overexpression of variants fails to rescue the pupal lethal phenotype of null mutations in Dmel\EMC1.
Amorphic and loss-of-function mutations of Dmel\EMC1 are lethal. Glial, but not neuronal, knockdown of Dmel\EMC1 is lethal at pupal stages. Ubiquitous overexpression of wild-type Dmel\EMC1 is lethal at pupal stages.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[CEREBELLAR ATROPHY, VISUAL IMPAIRMENT, AND PSYCHOMOTOR RETARDATION; CAVIPMR](https://omim.org/entry/616875)
[ENDOPLASMIC RETICULUM MEMBRANE PROTEIN COMPLEX, SUBUNIT 1; EMC1](https://omim.org/entry/616846)
Cerebellar atrophy, visual impairment, and psychomotor retardation is an autosomal recessive neurodegenerative disorder with global developmental delay, speech delay, and hypotonia associated with cerebellar atrophy and a short or atrophic corpus callosum. All patients had some variable dysmorphic features, including deep-set eyes, gingival hyperplasia, retrognathia, and short philtrum. Ophthalmologic abnormalities were also present, and included cortical visual impairment, abnormal visual evoked potentials (VEP) and electroretinograms (ERG), esotropia, strabismus, and astigmatism. Some patients also have a more severe disorder, with profound intellectual disability, progressive microcephaly, increased tone in the extremities, hyporeflexia, dystonic posturing, scoliosis, and cerebral atrophy (Harel et al., 2016; pubmed:26942288). [from MIM:616875; 2022.10.24]
Cerebellar atrophy, visual impairment, and psychomotor retardation (CAVIPMR) is caused by homozygous mutation in the EMC1 gene on chromosome 1p36. [from MIM:616875; 2022.10.24]
EMC1 is 1 of 10 subunits of an endoplasmic reticulum (ER) protein complex implicated in ER-mitochondria crosstalk, protein folding, and possibly elimination of misfolded membrane proteins (Harel et al., 2016; pubmed:26942288). [from MIM:616846; 2022.10.24]
One to one: human gene to Drosophila gene.
High-scoring ortholog of human EMC1 (1 Drosophila to 1 human).
