Activity
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| Mitochondrial disorders v9.23 | PDE12 |
Achchuthan Shanmugasundram changed review comment from: PMID:39567835 (2025) reported five cases (three live-borns and two foetuses) from three unrelated families presenting with severe early-onset mitochondrial disease. They showed wide-ranging clinical presentations in utero and within the neonatal period, with muscle and brain involvement leading to marked cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. In family 1, one of the two patients died at 3 months of age, while patient from family 2 died at day 2. Increased nuchal translucency, severe intra-uterine growth retardation, hydrops and cystic hygroma was noted in one of the two foetuses by prenatal ultrasound and the pregnancy ended spontaneously at 22 gestational weeks. Nuchal translucency and absence of foetal movements were observed in the other foetus, which was terminated at 19 weeks. All three families harboured a different homozygous variant in PDE12 gene (p.Tyr155Cys, p.Gly372Glu & p.Arg41Pro) as identified by whole-exome sequencing. Based on the gnomAD database, all three missense variants were reported to be rare in general population. Functional evidence from patient fibroblast studies showed reduced PDE12 protein and accumulation of abnormally polyadenylated mitochondrial tRNAs/rRNAs, causing disrupted mitochondrial RNA processing. In addition, in silico modeling of the variants also suggested loss of function. This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:39567835 (2025) reported five cases (three live-borns and two foetuses) from three unrelated families presenting with severe early-onset mitochondrial disease. They showed wide-ranging clinical presentations in utero and within the neonatal period, with muscle and brain involvement leading to marked cytochrome c oxidase (COX) deficiency in muscle and severe lactic acidosis. In family 1, one of the two patients died at 3 months of age, while patient from family 2 died at day 2. Increased nuchal translucency, severe intra-uterine growth retardation, hydrops and cystic hygroma was noted in one of the two foetuses from family 3 by prenatal ultrasound and the pregnancy ended spontaneously at 22 gestational weeks. Nuchal translucency and absence of foetal movements were observed in the other foetus, which was terminated at 19 weeks. All three families harboured a different homozygous variant in PDE12 gene (p.Tyr155Cys, p.Gly372Glu & p.Arg41Pro) as identified by whole-exome sequencing. Based on the gnomAD database, all three missense variants were reported to be rare in general population. Functional evidence from patient fibroblast studies showed reduced PDE12 protein and accumulation of abnormally polyadenylated mitochondrial tRNAs/rRNAs, causing disrupted mitochondrial RNA processing. In addition, in silico modeling of the variants also suggested loss of function. This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype. |
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| Mitochondrial disorders v9.23 | PDE12 |
Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: PDE12. Tag Q3_25_NHS_review tag was added to gene: PDE12. |
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| Mitochondrial disorders v9.23 | PDE12 | Achchuthan Shanmugasundram Classified gene: PDE12 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.23 | PDE12 | Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Karen Stals, there is sufficient evidence (three unrelated families and functional evidence) available for the association of biallelic variants in this gene with mitochondrial disease. Hence, this gene can be promoted to green rating in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.23 | PDE12 | Achchuthan Shanmugasundram Gene: pde12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.22 | PDE12 | Achchuthan Shanmugasundram Phenotypes for gene: PDE12 were changed from to mitochondrial disease, MONDO:0044970 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.21 | PDE12 | Achchuthan Shanmugasundram Publications for gene: PDE12 were set to 29903433; 28745585 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.20 | PDE12 | Achchuthan Shanmugasundram Mode of inheritance for gene: PDE12 was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.19 | PDE12 | Achchuthan Shanmugasundram reviewed gene: PDE12: Rating: GREEN; Mode of pathogenicity: None; Publications: 39567835; Phenotypes: mitochondrial disease, MONDO:0044970; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v9.19 | PDE12 | Karen Stals reviewed gene: PDE12: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:39567835; Phenotypes: Neonatal mitochondrial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v1.445 | PDE12 | Sarah Leigh Publications for gene: PDE12 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v1.423 | PDE12 | Sarah Leigh reviewed gene: PDE12: Rating: RED; Mode of pathogenicity: ; Publications: 29903433, 28745585; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mitochondrial disorders v1.422 | PDE12 |
Sarah Leigh gene: PDE12 was added gene: PDE12 was added to Mitochondrial disorders. Sources: Expert list Mode of inheritance for gene: PDE12 was set to |
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