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| Fetal anomalies v1.171 | MMP13 | Zornitza Stark Classified gene: MMP13 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.171 | MMP13 | Zornitza Stark Gene: mmp13 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.170 | MMP13 | Zornitza Stark reviewed gene: MMP13: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400); Mode of inheritance: BOTH monoallelic and 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 |
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| Fetal anomalies v0.655 | MMP13 | Zornitza Stark Marked gene: MMP13 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.655 | MMP13 | Zornitza Stark Gene: mmp13 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.655 | MMP13 | Zornitza Stark Phenotypes for gene: MMP13 were changed from SPONDYLOEPIMETAPHYSEAL DYSPLASIA MISSOURI TYPE; METAPHYSEAL ANADYSPLASIA TYPE 1 to Metaphyseal anadysplasia 1 (MIM#602111); Metaphyseal dysplasia, Spahr type (MIM#250400) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.654 | MMP13 | Zornitza Stark Publications for gene: MMP13 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.653 | MMP13 | Zornitza Stark Mode of pathogenicity for gene: MMP13 was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. |
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| Fetal anomalies v0.584 | MMP13 | Daniel Flanagan reviewed gene: MMP13: Rating: GREEN; Mode of pathogenicity: Other; Publications: 19615667, 24781753, 24648384; Phenotypes: Metaphyseal anadysplasia 1 (MIM#602111), Metaphyseal dysplasia, Spahr type (MIM#250400), ?Spondyloepimetaphyseal dysplasia, Missouri type (MIM#602111); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.0 | MMP13 |
Zornitza Stark gene: MMP13 was added gene: MMP13 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: MMP13 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: MMP13 were set to SPONDYLOEPIMETAPHYSEAL DYSPLASIA MISSOURI TYPE; METAPHYSEAL ANADYSPLASIA TYPE 1 |
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