Skeletal dysplasia
Gene: MIA3
Comment on list classification: Promoting this gene from grey to red based on 1 family reported so far.Created: 20 Jan 2021, 12:09 p.m. | Last Modified: 20 Jan 2021, 12:09 p.m.
Panel Version: 2.52
As described by the Expert Reviewer Lekszas et al 2020 (PMID:32101163) reports a consanguineous Turkish family with 4 sons who presented with a variety of phenotypes including growth retardation, proportionate short stature, clinodactyly of the fifth finger, brachydactyly, platyspondyly of relevance to the skeletal dysplasia panel. A homozygous synonymous substitution in MIA3 was found in all affected family members, with parents being heterozygous. RNA analysis from patient blood samples showed that the variant results in exon eight skipping leading to a truncated protein. Functional studies found this results in reduced collagen expression in U2OS cells.Created: 20 Jan 2021, noon | Last Modified: 20 Jan 2021, noon
Panel Version: 2.50
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
dentinogenesis imperfecta; short stature; brachydactyly; Platyspondyly; insulin-dependent diabetes mellitus; sensorineural hearing loss; mild intellectual disability
Publications
The MIA3 gene is synonymous with TANGO1 in PMID:32101163. This publication reports a synonymous substitution (NM_001324062.1:c.3621A > G) that results in functionally validated exon eight skipping, leading to a truncated TANGO1/MIA3 protein. The variant was identified in four homozygous affected sibs of a consanguineous family, that presented with severe dentinogenesis imperfecta, short stature, various skeletal abnormalities, insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. Functional studies in HeLa and U2OS cells revealed that the truncated TANGO1/MIA3 protein is dispersed in the ER and its expression in cells with intact endogenous TANGO1/MIA3 impairs cellular collagen I secretion (PMID:32101163).
Sources: LiteratureCreated: 16 Dec 2020, 2:23 p.m. | Last Modified: 16 Dec 2020, 2:24 p.m.
Panel Version: 2.36
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
short stature; skeletal dysplasia; amelogenesis
Publications
Gene: mia3 has been classified as Red List (Low Evidence).
Phenotypes for gene: MIA3 were changed from short stature; skeletal dysplasia; amelogenesis to short stature; skeletal dysplasia; amelogenesis; dentinogenesis imperfecta; short stature; brachydactyly; Platyspondyly; insulin-dependent diabetes mellitus; sensorineural hearing loss; mild intellectual disability
gene: MIA3 was added gene: MIA3 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIA3 were set to 32101163 Phenotypes for gene: MIA3 were set to short stature; skeletal dysplasia; amelogenesis Penetrance for gene: MIA3 were set to unknown Review for gene: MIA3 was set to RED