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Intellectual disability v9.400 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. Severe developmental delay/ intellectual disability was reported in all ten patients. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Karen Stals, there are ten patients from five unrelated families reported with biallelic PGBD5 variants and neurodevelopmental disorder. Severe developmental delay/ intellectual disability was reported in all ten patients. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v9.400 PGBD5 Achchuthan Shanmugasundram Classified gene: PGBD5 as Amber List (moderate evidence)
Intellectual disability v9.400 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. Severe developmental delay/ intellectual disability was reported in all ten patients. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v9.400 PGBD5 Achchuthan Shanmugasundram Gene: pgbd5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.399 PGBD5 Achchuthan Shanmugasundram Phenotypes for gene: PGBD5 were changed from Seizures; global developmental delay; spasticity; hypotonia to Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482; neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO:0980968
Intellectual disability v9.398 PGBD5 Achchuthan Shanmugasundram edited their review of gene: PGBD5: Changed phenotypes to: Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482, neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO:0980968
Intellectual disability v9.398 PGBD5 Achchuthan Shanmugasundram Publications for gene: PGBD5 were set to PMID: 41533792
Intellectual disability v9.397 PGBD5 Achchuthan Shanmugasundram Tag Q2_26_promote_green tag was added to gene: PGBD5.
Tag Q2_26_NHS_review tag was added to gene: PGBD5.
Intellectual disability v9.397 PGBD5 Achchuthan Shanmugasundram commented on gene: PGBD5: 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.
Intellectual disability v9.397 PGBD5 Achchuthan Shanmugasundram reviewed gene: PGBD5: Rating: GREEN; Mode of pathogenicity: None; Publications: 41533792; Phenotypes: Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482, neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO_0980968; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.389 PGBD5 Karen Stals gene: PGBD5 was added
gene: PGBD5 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PGBD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGBD5 were set to PMID: 41533792
Phenotypes for gene: PGBD5 were set to Seizures; global developmental delay; spasticity; hypotonia
Penetrance for gene: PGBD5 were set to Complete
Review for gene: PGBD5 was set to GREEN
gene: PGBD5 was marked as current diagnostic
Added comment: Zapater et al. 2026 PMID:41533792 report 5 families with homozygous loss of function variants in PGBD5 co-segregating in two affected siblings in each family (variants identified via whole exome sequencing). Authors show that PGBD5 contributes to normal brain development in mice and humans.
Sources: Literature