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Fetal anomalies v0.887 MMP9 Zornitza Stark Marked gene: MMP9 as ready
Fetal anomalies v0.887 MMP9 Zornitza Stark Gene: mmp9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.887 MMP9 Zornitza Stark Classified gene: MMP9 as Amber List (moderate evidence)
Fetal anomalies v0.887 MMP9 Zornitza Stark Gene: mmp9 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v0.886 MMP9 Zornitza Stark reviewed gene: MMP9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 2 - MIM# 613073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.886 MMP9 Krithika Murali gene: MMP9 was added
gene: MMP9 was added to Fetal anomalies. Sources: Expert list,Literature
Mode of inheritance for gene: MMP9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP9 were set to 19615667; 28342220; 34407464
Phenotypes for gene: MMP9 were set to Metaphyseal anadysplasia 2 - MIM# 613073
Review for gene: MMP9 was set to GREEN
Added comment: 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.

Borderline amber-green gene in the prenatal setting based on current evidence.
Sources: Expert list, Literature
Fetal anomalies v0.587 MMP13 Daniel Flanagan changed review comment from: At least 7 families described with either mono or biallelic variants reports.
Autosomal dominant metaphyseal anadysplasia has been described as more severe, with dominant-negative missense mutations in the prodomain of MMP13 that determine autoactivation of MMP13 and intracellular degradation of both MMP13 and MMP9, resulting in a double enzymatic deficiency. Recessive metaphyseal anadysplasia has been described as a milder form, caused by biallelic loss of function of either MMP9 or MMP13.; to: At least 7 families described with either mono (Metaphyseal anadysplasia) or biallelic (Metaphyseal dysplasia, Spahr type) variants reports.
Autosomal dominant metaphyseal anadysplasia has been described as more severe, with dominant-negative missense mutations in the prodomain of MMP13 that determine autoactivation of MMP13 and intracellular degradation of both MMP13 and MMP9, resulting in a double enzymatic deficiency. Recessive metaphyseal anadysplasia has been described as a milder form, caused by biallelic loss of function of either MMP9 or MMP13.