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| Hereditary ataxia with onset in adulthood v3.16 | PRDX3 | Achchuthan Shanmugasundram Phenotypes for gene: PRDX3 were changed from Cerebellar ataxia (early onset, mild to moderate, progressive) to Spinocerebellar ataxia, autosomal recessive 32, OMIM:619862 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v3.10 | PRDX3 | Mafalda Gomes Tag Q1_22_rating was removed from gene: PRDX3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v3.10 | PRDX3 | Mafalda Gomes reviewed gene: PRDX3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v3.9 | PRDX3 |
Mafalda Gomes Source NHS GMS was added to PRDX3. Source Expert Review Green was added to PRDX3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Hereditary ataxia with onset in adulthood v2.138 | PRDX3 | Arina Puzriakova Tag Q1_22_rating tag was added to gene: PRDX3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v2.138 | PRDX3 | Arina Puzriakova Classified gene: PRDX3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v2.138 | PRDX3 |
Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to promote this gene to Green at the next GMS panel update. Rebelo et al., 2021 (PMID: 33889951) reported five simplex families with biallelic variants in PRDX3 leading to complete loss of its encoded protein. Clinical presentation in all individuals predominantly consisted of gait and upper limb ataxia and cerebellar atrophy. Age of onset was at 13, 15, 21, 22 and 23 years of age. Pathogenicity supported by molecular studies using patient fibroblasts, cerebellar medulloblastoma cells and Drosophila. |
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| Hereditary ataxia with onset in adulthood v2.138 | PRDX3 | Arina Puzriakova Gene: prdx3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary ataxia with onset in adulthood v2.81 | PRDX3 |
Zornitza Stark gene: PRDX3 was added gene: PRDX3 was added to Hereditary ataxia - adult onset. Sources: Literature Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRDX3 were set to 33889951 Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive) Review for gene: PRDX3 was set to GREEN gene: PRDX3 was marked as current diagnostic Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex. Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres. The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism. The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense, suggestive of founder effect. Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated. Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species. In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress. Sources: Literature |
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