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| Ataxia and cerebellar anomalies - narrow panel v8.85 | PGBD5 | Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Karen Stals, there are ten patients from five unrelated families reported with biallelic PGBD5 variants and a neurodevelopmental disorder. Ataxia was reported in seven patients from four of these five families. Cerebellar atrophy was also reported in some patients. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: There are ten patients from five unrelated families reported with biallelic PGBD5 variants and neurodevelopmental disorder. Ataxia was reported in seven patients from four of these five families. Cerebellar atrophy was also reported in some patients. There is also functional evidence available in support of the association. Hence, this gene can be promoted to green rating in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.85 | PGBD5 | Achchuthan Shanmugasundram Classified gene: PGBD5 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.85 | PGBD5 | Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Karen Stals, there are ten patients from five unrelated families reported with biallelic PGBD5 variants and a neurodevelopmental disorder. Ataxia was reported in seven patients from four of these five families. Cerebellar atrophy was also reported in some patients. Hence, this gene can be promoted to green rating in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.85 | PGBD5 | Achchuthan Shanmugasundram Gene: pgbd5 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v8.84 | PGBD5 |
Achchuthan Shanmugasundram gene: PGBD5 was added gene: PGBD5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Q2_26_promote_green tags were added to gene: PGBD5. Mode of inheritance for gene: PGBD5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PGBD5 were set to 41533792 Phenotypes for gene: PGBD5 were set to Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482; neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO:0980968 Review for gene: PGBD5 was set to GREEN Added comment: PMID:41533792 (2026) reported the identification of genetic variants in PGBD5 gene using GeneMatcher in ten individuals from five unrelated consanguineous families. Exome sequencing was used to identify distinct homozygous PGBD5 variants segregating with the affected family members and this was confirmed by Sanger sequencing. These affected children shared conserved clinical phenotypes across neurodevelopmental and motor domains. Neurodevelopmental features included intellectual disability and developmental delay (ID/DD; ten of ten), epilepsy (nine of nine), limited or no speech (nine of nine), autism spectrum disorder, or social delay (ASD; four of six). Prominent motor features included axial hypotonia (nine of nine), increased peripheral tone (seven of nine) or decreased peripheral tone (two of nine), increased tendon reflexes (five of nine), or decreased tendon reflexes (four of nine). Other observed neurological phenotypes include spasticity that mainly affected the lower limbs (five of nine), intermittent dystonia (three of ten), and ataxia (seven of ten). There is also evidence available from Pgbd5-null mice, which were runted and had significantly smaller brains compared to wildtype. Mutant mice showed increased locomotor activity, reduced anxiety-like behavior, impaired motor coordination, increased susceptibility to seizures, and decreased cortical volume on brain MRI. Analysis of neurons derived from Pgbd5-null mouse brains showed reduced DNA breakage and repair in postmitotic neuronal precursors during cortical development compared to controls. This gene has already been associated with relevant phenotype in OMIM (MIM #41533792, last accessed 28 April 2026), but not yet in Gene2Phenotype. Sources: Literature |
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