Skeletal dysplasia
Gene: MATN3
Multiple epiphyseal dysplasia & psudoachondroplasia gp of SD / spondylo-epi-(meta)-physeal dysplasias gp of SD. AT least 3 unrelated cases.; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epiphyseal dysplasia, multiple, 5, 607078; Spondyloepimetaphyseal dysplasia, 608728
Comment on list classification: More than 3 cases of variants in this gene in patients with a relevant phenotype.Created: 17 Jul 2019, 12:37 p.m. | Last Modified: 17 Jul 2019, 12:37 p.m.
Panel Version: 1.179
Comment on mode of inheritance: Leaving mode of inheritance as monoallelelic, as only one case reported of biallelic variants causing Spondyloepimetaphyseal Dysplasia so far.Created: 17 Jul 2019, 12:37 p.m. | Last Modified: 17 Jul 2019, 12:37 p.m.
Panel Version: 1.178
Associated with Spondyloepimetaphyseal dysplasia (#608728) and Epiphyseal dysplasia, multiple, 5 (#607078) in OMIM.
Epiphyseal dysplasia:
PMID: 11479597 - Chapman et al. 2001 - 1 family - 2 different missense mutations (V194D and R121W) identified. Suggested it might be a dominant negative mode of action.
PMID: 14729835 - Jackson et al. 2004 - in 7 families with multiple epiphyseal dysplasia they identified 4 novel mutations and 1 recurrent mutation ( R121W).
PMID: PMID: 30080953 - Pettersson et al 2018 - in a 17‐year‐old girl born to healthy, nonconsanguineous parents of Caucasian origin who was diagnosed with multiple epiphyseal dysplasia they identified a heterozygous intragenic duplication within MATN3, affecting exons 2–5 by custom array‐CGH.
Spondyloepimetaphyseal Dysplasia:
PMID: 15121775 - Borochowitz et al. 2004 - report a large consanguineous Arab Muslim family with autosomal recessive spondyloepimetaphyseal dysplasia with a homozygous missense mutation in MATN3.
Animal studies - PMID: 16199550 - Otten et al. 2005 - mice with point mutations corresponding to human disease-causing mutations were created and found that transcripts for two of mutation were poorly expressed and protein trafficking was reduced. PMID: 16287128 - Cotterill et al. 2005 - experiments with wild type and mutant protein expressed in Chinese hamster ovaries showed intracellular retention of the mutant protein.Created: 17 Jul 2019, 12:27 p.m. | Last Modified: 17 Jul 2019, 12:33 p.m.
Panel Version: 1.177
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: MATN3; Initial rating suggestion: greenCreated: 6 Mar 2019, 11:36 a.m.
Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve AbbsCreated: 27 Jul 2016, 9:44 a.m.
Tier 1Created: 17 Jun 2016, 8:05 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Epiphyseal dysplasia, multiple, 5 607078; Spondyloepimetaphyseal dysplasia 608728; {Osteoarthritis susceptibility 2} 140600
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: MATN3 were set to
Gene: matn3 has been classified as Green List (High Evidence).
Mode of inheritance for gene: MATN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Spondyloepimetaphyseal dysplasia, 608728; Epiphyseal dysplasia, multiple, 5, 607078 for gene: MATN3
Source NHS GMS was added to MATN3. Rating Changed from Green List (high evidence) to Red List (low evidence)
Promoted to version 1 9th August 2016
MATN3 was added to Unexplained skeletal dysplasiapanel. Source: Expert Review Red
MATN3 was added to Unexplained skeletal dysplasiapanel. Source: Illumina TruGenome Clinical Sequencing Services MATN3 was added to Unexplained skeletal dysplasiapanel. Source: Emory Genetics Laboratory MATN3 was added to Unexplained skeletal dysplasiapanel. Source: Radboud University Medical Center, Nijmegen MATN3 was added to Unexplained skeletal dysplasiapanel. Source: Expert Review Green Model of inheritance for gene MATN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
MATN3 was added to Unexplained skeletal dysplasiapanel. Sources:
MATN3 was created by sleigh