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| Mendeliome v1.2202 | PDE12 | Zornitza Stark Marked gene: PDE12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2202 | PDE12 | Zornitza Stark Gene: pde12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2202 | PDE12 | Zornitza Stark Phenotypes for gene: PDE12 were changed from Mitochondrial disease MONDO:0044970 to Mitochondrial disease MONDO:0044970, PDE12-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2201 | PDE12 | Chirag Patel Classified gene: PDE12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2201 | PDE12 | Chirag Patel Gene: pde12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2199 | PDE12 |
Chirag Patel gene: PDE12 was added gene: PDE12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE12 were set to PMID: 39567835 Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970 Review for gene: PDE12 was set to GREEN Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death). -Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle. -Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron transfer chain activities in fibroblasts. -Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V). WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity. PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein. Sources: Literature |
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