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Early onset or syndromic epilepsy v8.61 BSN Helen Lord gene: BSN was added
gene: BSN was added to Early onset or syndromic epilepsy. Sources: Other
Mode of inheritance for gene: BSN was set to Unknown
Publications for gene: BSN were set to PMID: 36600631; 39616287; 40393460
Phenotypes for gene: BSN were set to Seizures - different types
Penetrance for gene: BSN were set to unknown
Review for gene: BSN was set to AMBER
Added comment: There are a lot of cases to support an AD phenotype but unsure as to whether there is also an AR pheontype associated with disease...

PMID:36600631 - Ye et al, 2023:
BSN gene encodes the Bsssoon protein which is highly expressed in the mammalian brain especially the cerebral cortex and the hippocampus.
WES in 313 trios with epilepsies of unknown causes novel BSN variants identifed in 5 cases and 3 additional variants identified in 3 cases from different centres:
Cases 1-4 compound het - variants shown to be inherited in trans
Cases 5-8 - het variants idenitied in case 5 & 6 inherited from affected parent (febrile seizure in these parents) and in cases 7 & 8 - arise de novo.
The 9 variants present in low or no allele freq in all populations or East Asian populations - no hom in gnomAD. No other pathogenic/likely pathogenic variants in other epilepsy genes identiifed.
Fig 3:
B:The 2 nonsense variants in exon 5 thought to result in the truncation of the basson protein and trigger NMD. Both de novo. They state LOF and haploinsuffucency of BSN are potentially pathogenic.
C: 6/9 missense variants led to hydrogen bond alterations - mostly creation of hydrogen bonds which were not predicted orignally. 5/9 missense variants clustered in the C-terminus. Among the 4 pairs of compound het variants at least 1 variant in each pair had hydrogen bond alterations.
In the discussion they state LOF of Bassoon is potentially the underlying mechanism of pathogenicity of BSN variants, which is consistent with the pathogenisi of other genes encoding CAZ proteins such as UNC13A and UNC13B; however, the functional effects of BSN variants warrants further investigation.
In het BSN knockout mice - no phenotype; however, hom knockout mice null led to spontaneous seizures and partial preamture lethality. Clinically the patients with monoallelic BSN missense variants achieved seizure free status without treatment or under monotherapy; whereas, the majority of patients with biallelic missense variants required combination therapy, possible correlation between genotype and phenotype severity.

PMID 39616287: Yacoub et al, 2025: WES in 10 JME (juvenille myoclonic epilepsy) patients - P4 found to have a het BSN missense variant - c.2534G>A p.(Arg845Gln), also identified in her affected brother who has GTCs, but also detected in an unaffected brother. Presumably also inherited from an unaffected pedogree (pedigree included - no mention of parental testing).

PMID: 40393460 Guzman et al, 2025: cohort of 29 individuals with BSN variants including 14 with de novo vairants, 13 individuals with PTVs (protein truncating variants) of unknown inheritance and 2 individuals with PTVs with paternal inheritance. Affected individuals had diverse neurodevelopmental phenotypes including behavioural abnormalities; delayed speech, learning difficulties and variable seizure types.
Recruitment: 2/29 - enrolled in the Epilepsy genetics research project at Childrens Hospital Philadelphia (CHOP) confirmed de novo; 14/29 identified via gene matcher - 9/14 confirmed de novo by respective institutions; 7/29 identified through Penn medicine biobank; 1/29 missense de novo BSN variant identified from birth defects biorepositary at CHOP; 3/29 BSN PTVs idenitifed through the center for applied genomics at CHOP and a lit review identified 2/29 previously reported individuals with de novo PTVs in BSN.
Table 1 details the 14 individuals with de novo BSN variants - 8/14 had seizures (different types); 12/14 had developmental features.
They suggest haploinsuffucency as as a likely mechanism.
Sources: Other
Early onset or syndromic epilepsy v1.412 GLYCTK Rebecca Foulger commented on gene: GLYCTK: PMID:28462797 (Swanson et al., 2017) reviewed the Serbian patient from Sass et al., 2010. In addition to p.Phe483SerfsX2 variant in GLYCTK, the patient had an additional Ser117Leu variant in AMT highlighting the co-occurence of two metabolic conditions (D-glyceric aciduria and nonketotic hyperglycinemia).
Early onset or syndromic epilepsy v1.191 GAMT Rebecca Foulger Source Wessex and West Midlands GLH was added to GAMT.
Early onset or syndromic epilepsy v1.191 AMT Rebecca Foulger Source Wessex and West Midlands GLH was added to AMT.
Early onset or syndromic epilepsy v1.190 GAMT Rebecca Foulger Source NHS GMS was added to GAMT.
Early onset or syndromic epilepsy v1.190 AMT Rebecca Foulger Source NHS GMS was added to AMT.
Early onset or syndromic epilepsy v1.189 GAMT Rebecca Foulger reviewed gene: GAMT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v1.189 AMT Rebecca Foulger reviewed gene: AMT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v1.188 GAMT Tracy Lester reviewed gene: GAMT: Rating: GREEN; Mode of pathogenicity: ; Publications: 19027335; Phenotypes: Cerebral creatine deficiency syndrome, 612736; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v1.188 AMT Tracy Lester reviewed gene: AMT: Rating: GREEN; Mode of pathogenicity: ; Publications: 25231368; Phenotypes: Glycine encephalopathy, 605899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1046 GAMT Louise Daugherty Marked gene: GAMT as ready
Early onset or syndromic epilepsy v0.1046 GAMT Louise Daugherty Gene: gamt has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1044 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase; GAMT deficiency
Early onset or syndromic epilepsy v0.1043 GAMT Louise Daugherty Publications for gene: GAMT were set to 15651030; 17101918; 15108290; 19027335
Early onset or syndromic epilepsy v0.1042 GAMT Louise Daugherty Classified gene: GAMT as Green List (high evidence)
Early onset or syndromic epilepsy v0.1042 GAMT Louise Daugherty Gene: gamt has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1041 GAMT Louise Daugherty Publications for gene: GAMT were set to
Early onset or syndromic epilepsy v0.1039 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase
Early onset or syndromic epilepsy v0.1038 GAMT Louise Daugherty Mode of inheritance for gene: GAMT was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1037 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from to Cerebral creatine deficiency syndrome 2, 612736; Seizures
Early onset or syndromic epilepsy GAMT Zornitza Stark reviewed gene: GAMT
Early onset or syndromic epilepsy AMT Sarah Leigh marked gene: AMT as ready
Early onset or syndromic epilepsy AMT Sarah Leigh classified AMT as Green List (high evidence)
Early onset or syndromic epilepsy AMT Arianna Tucci reviewed gene: AMT
Early onset or syndromic epilepsy AMT Sarah Leigh Added gene to panel