| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Early onset or syndromic epilepsy v2.491 | UGDH | Sarah Leigh Tag for-review was removed from gene: UGDH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.491 | UGDH | Sarah Leigh commented on gene: UGDH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.490 | UGDH |
Sarah Leigh Source Expert Review Green was added to UGDH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Early onset or syndromic epilepsy v2.158 | UGDH | Arina Puzriakova Classified gene: UGDH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.158 | UGDH |
Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update. Multiple patients from over 20 unrelated families with severe epilepsy, mostly ranging from neonatal to infantile onset developmental epileptic encephalopathy. |
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| Early onset or syndromic epilepsy v2.158 | UGDH | Arina Puzriakova Gene: ugdh has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.157 | UGDH | Arina Puzriakova Tag for-review tag was added to gene: UGDH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.47 | UGDH |
Konstantinos Varvagiannis gene: UGDH was added gene: UGDH was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: UGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UGDH were set to 32001716 Phenotypes for gene: UGDH were set to Epileptic encephalopathy, early infantile, 84 - MIM #618792 Penetrance for gene: UGDH were set to Complete Review for gene: UGDH was set to GREEN Added comment: Hengel et al (2020 - PMID: 32001716) report on 36 individuals with biallelic UGDH pathogenic variants. The phenotype corresponded overall to a developmental epileptic encephalopathy with hypotonia, feeding difficulties, severe global DD, moderate or commonly severe ID in all. Hypotonia and motor disorder (incl. spasticity, dystonia, ataxia, chorea, etc) often occurred prior to the onset of seizures. A single individual did not present seizures and 2 sibs had only seizures in the setting of fever. Affected subjects were tested by exome sequencing and UGDH variants were the only/best candidates for the phenotype following also segregation studies. Many were compound heterozygous or homozygous (~6 families were consanguineous) for missense variants and few were compound heterozygous for missense and pLoF variants. There were no individuals with biallelic pLoF variants identified. Parental/sib studies were all compatible with AR inheritance mode. UGDH encodes the enzyme UDP-glucose dehydrogenase which converts UDP-glucose to UDP-glucuronate, the latter being a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate [OMIM]. Patient fibroblast and biochemical assays suggested a LoF effect of variants leading to impairment of UGDH stability, oligomerization or enzymatic activity (decreased UGDH-catalyzed reduction of NAD+ to NADH / hyaluronic acid production which requires UDP-glucuronate). Attempts to model the disorder using an already developped zebrafish model (for a hypomorphic LoF allele) were unsuccessful as fish did not exhibit seizures spontaneously or upon induction with PTZ. Modelling of the disorder in vitro using patient-derived cerebral organoids demonstrated smaller organoids due to reduced number of proliferating neural progenitors. Sources: Literature |
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