Skeletal dysplasia

Gene: MATN3

Green List (high evidence)

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 Lester

Created: 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

I don't know

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: green

Created: 6 Mar 2019, 11:36 a.m.

Green List (high evidence)

Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve Abbs

Created: 27 Jul 2016, 9:44 a.m.

Green List (high evidence)

Tier 1

Created: 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