Skeletal dysplasia

Gene: MMP9

Green List (high evidence)

Comment on list classification: There are now 4 unrelated individuals reported with biallelic MMP9 variants and Metaphyseal anadysplasia. Hence, this gene can be promoted to Green at the next update.

Created: 13 Aug 2026, 11:58 a.m. | Last Modified: 13 Aug 2026, 11:58 a.m.

Panel Version: 10.3

PMID: 36035187 Cheng et al., 2022
Report of a fetus with Metaphyseal Anadysplasia Type 2 (short femur, unilateral absence of fibula, and short curvature of the tibia), harbouring comp het variants in MMP9: NM_004994.3: c.151C>T, p.Arg51Cys and c.929del, p.Gly310Alafs*28. Seq method: Trio exome + Sanger seq. The parents were non-consanguineous and healthy.

PMID: 34407464 Bonilla-Fornés et al., 2021
Report of a young Spanish boy, born to consanguineous parents, referred at 19 months old for abnormal gait due to bowed legs. Clinical and radiological examination revealed scoliosis, genu varum and metaphyseal abnormalities. A homozygous MMP9 nonsense variant, NM_004994.2:c.1764G>A; p.(Trp588*) was identified.

MMP9 is associated with AR Metaphyseal anadysplasia 2, OMIM:613073 in OMIM (accessed 13th Aug 2026).

Created: 13 Aug 2026, 11:52 a.m. | Last Modified: 13 Aug 2026, 11:52 a.m.

Panel Version: 10.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metaphyseal anadysplasia 2, OMIM:613073; metaphyseal anadysplasia 2, MONDO:0013113

Publications

• 34407464
• 36035187

Green List (high evidence)

Metaphyseal dysplasia gp of SD - at least 3 cases reported; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metaphyseal anadysplasia 2 613073

Publications

• 19615667
• 28342220
• 24781753

I don't know

Comment on list classification: Changing rating from red to amber as two cases have been reported with variants in this gene.

Created: 17 Jul 2019, 12:42 p.m. | Last Modified: 17 Jul 2019, 12:42 p.m.

Panel Version: 1.181

Associated with Metaphyseal anadysplasia 2 (613073) in OMIM

PMID: 19615667 - Lausch et al 2009 - 1 family. In a recessive kindred, family E, MMP13 was normal, but a c.21T>A transversion in exon 1 altered the start codon of MMP9, substituting methionine with lysine. The variant segregated with the disease in the family.

PMID: 28342220 - Sharony et al 2017 - 1 family. Two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses. NM_004994: c.[559C>T], p.(L187F).

PMID: 24781753 - Li et al 2015 - 0 families. 2 brothers with short stature and mixed epiphyseal and metaphyseal dysplasia. Identified a homozygous C>T transition mutation in exon 2 of MMP13 (c.325C>T, p.(R109*). So not in MMP9.

Summary: only 2 cases reported, 3rd had variant in MMP13 not MMP9.

Mouse model - PMID: 9590175 - Vu et al. 1998 - report that homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification.

Created: 8 May 2019, 2:44 p.m. | Last Modified: 31 Jul 2019, 12:38 p.m.

Panel Version: 1.192

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: MMP9; Initial rating suggestion: green

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

Comment when marking as ready: Only one variant identified in this phenotype

Created: 12 Jul 2016, 10:04 a.m.

Comment on list classification: Only one variant identified in this phenotype

Created: 11 Jul 2016, 8:29 a.m.

Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)

Created: 21 Jun 2016, 12:58 p.m.

Green List (high evidence)

Tier 1

Created: 17 Jun 2016, 8:06 a.m.

Mode of inheritance
Unknown

Phenotypes
Metaphyseal anadysplasia 2 613073

Variants in this GENE are reported as part of current diagnostic practice