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Skeletal dysplasia

Gene: MMP9

Green List (high evidence)

MMP9 (matrix metallopeptidase 9)
EnsemblGeneIds (GRCh38): ENSG00000100985
EnsemblGeneIds (GRCh37): ENSG00000100985
OMIM: 120361, Gene2Phenotype
MMP9 is in 5 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Biallelic variants in MMP9 associated with autosomal recessive, metaphyseal anadysplasia type 2. Usually associated with a milder phenotype characterised by normal birth length, transitory bowing of the legs, spontaneous regression and disappearance of metaphyseal alterations during adolescence. Phenotype of MAD type 2 cases secondary to biallelic MMP13 gene mutations (more reported cases associated with this gene) similar to MMP9 associated cases.

MMP9-associated MAD type 2 cases reported so far:

x2 sibs from 1 consanguineous Pakistani family diagnosed postnatally with normal stature, genu varum, metaphyseal fraying during infancy (PMID 19615667)

x1 child from consanguineous family with homozygous nonsense variants diagnosed age 19 months with improvement of skeletal manifestations over a short period and by an early age (PMID 34407464)

x2 siblings from x1 non-consanguineous Jewish Caucasian family reported with more severe phenotype than other previously reported cases for MAD type 2 (PMID 28342220). Both siblings diagnosed during 2nd trimester with shortening of long bones. x1 fetus terminated at 19 weeks gestation - dysmorphic face including micrognathia, flattened nose, hypertelorism, short neck and hypoplastic lungs. 2nd liveborn female - reduced body length at birth (-4 SD), facial dysmorphism, cleft palate, anteriorly placed anus and other anomalies. No radiographic metaphyseal anomalies. Both children identified as having the same homozygous MMP9 missense variants. Authors acknowledge the phenotype is more severe than other previously reported cases of MAD type 2 associated with MMP9 or MMP13 gene variants. Some dispute regarding this prenatal case as detailed by PMID 34407464 such as possibility of an alternative skeletal dysplasia diagnosis (Desbuquois dypslasia type 2) and presence of 5 homozygotes in gnomad with the same missense variants - ?founder mutation.
Created: 2 Dec 2021, 5:10 a.m. | Last Modified: 2 Dec 2021, 5:10 a.m.
Panel Version: 0.9993

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metaphyseal anadysplasia 2, MIM# 613073

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review Green
  • Victorian Clinical Genetics Services
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • NHS GMS
  • Expert list
  • Emory Genetics Laboratory
  • Victorian Clinical Genetics Services
Phenotypes
  • 613073METAPHYSEAL ANADYSPLASIA 2
  • Metaphyseal anadysplasia 2 613073
OMIM
120361
Clinvar variants
Variants in MMP9
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 May 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: mmp9 has been classified as Green List (High Evidence).

26 May 2020, Gel status: 3

Set Phenotypes, Set publications

Tiong Tan (Victorian Clinical Genetics Services)

Added phenotypes 613073METAPHYSEAL ANADYSPLASIA 2 for gene: MMP9 Publications for gene MMP9 were updated from 28342220; 19615667 to 28342220; 19615667

26 May 2020, Gel status: 3

Set Phenotypes, Set publications

Tiong Tan (Victorian Clinical Genetics Services)

Added phenotypes 613073METAPHYSEAL ANADYSPLASIA 2 for gene: MMP9 Publications for gene MMP9 were updated from 19615667; 28342220 to 28342220; 19615667

26 May 2020, Gel status: 3

Added New Source, Added New Source, Set mode of inheritance, Set Phenotypes, Set publications, Status Update

Tiong Tan (Victorian Clinical Genetics Services)

Source Victorian Clinical Genetics Services was added to MMP9. Source Expert Review Green was added to MMP9. Mode of inheritance for gene MMP9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes 613073METAPHYSEAL ANADYSPLASIA 2 for gene: MMP9 Publications for gene MMP9 were updated from 28342220; 19615667 to 19615667; 28342220 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

17 Dec 2019, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: MMP9 was added gene: MMP9 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Amber,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: MMP9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MMP9 were set to 28342220; 19615667 Phenotypes for gene: MMP9 were set to Metaphyseal anadysplasia 2 613073