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| Mendeliome v1.3523 | RRP12 | Zornitza Stark Marked gene: RRP12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3523 | RRP12 | Zornitza Stark Gene: rrp12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3523 | RRP12 | Zornitza Stark Phenotypes for gene: RRP12 were changed from Brain calcifications to Syndromic disease, MONDO:0002254, RRP12-related; Brain calcifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3522 | RRP12 | Zornitza Stark Mode of pathogenicity for gene: RRP12 was changed from Other to None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3521 | RRP12 | Zornitza Stark Classified gene: RRP12 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3521 | RRP12 | Zornitza Stark Gene: rrp12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.3520 | RRP12 |
Catherine Dalzell gene: RRP12 was added gene: RRP12 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RRP12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RRP12 were set to PMID: 41059649 Phenotypes for gene: RRP12 were set to Brain calcifications Penetrance for gene: RRP12 were set to unknown Mode of pathogenicity for gene: RRP12 was set to Other Review for gene: RRP12 was set to AMBER Added comment: Variants: 5 individuals from 3 unrelated families with homozygous RRP12 variants (3 different variants, 2 consanguineous families with same variant, 2 siblings with same variant). Phenotype: all individuals had brain calcifications (varying distribution, severity and age of onset). The patients from the two consanguineous families both had infantile-onset generalised dystonia, spasticity and severe speech impairment with widespread brain calcifications. One also had microcephaly, seizures and a cataract whilst the other had mild thrombocytopenia. The two siblings had psychiatric symptoms (one bipolar disease and one anxiety) with marked, bilateral symmetric calcifications. One also had cerebellar ataxia, choreic movements, cognitive impairment and subtle Parkinsonism whilst the other had chronic tinnitus. The final individual had dizziness and only faint bilateral lenticular calcifications. Functional data: a statistically significant reduction in RRP12 protein levels in probands’ fibroblasts compared to controls was demonstrated. rrp12 knockdown in zebrafish embryos demonstrated reduced survival (50% survival at 2 days and maximum survival of 6 days compared to 100% survival at 6 days in controls). Phenotype abnormalities (delayed development and crimping) were also seen in the rrp12 knockdown embryos. Functional studies support a possible LoF mechanism. Sources: Literature |
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