TY  - JOUR
AB  - PURPOSE: ADAM23 is involved in neuronal excitability and interacts with LGI1, a known genetic risk factor for focal epilepsy. While ADAM23 has been linked to canine seizures, a recent gene-burden meta-analysis first nominated it as a risk gene for epilepsy in humans. Building on these findings, our study aimed to explore the significance of truncating ADAM23 variants in deeply phenotyped individuals with diverse seizure disorders. METHODS: We screened the exome sequencing data from 389 individuals with various seizure phenotypes for truncating variants in ADAM23. This report focuses on one individual harboring a heterozygous frameshift variant in ADAM23, selected for detailed analysis due to intriguing additional genetic findings. RESULTS: We identified a heterozygous frameshift variant (c.428del, p.Asn143Ilefs*26) in ADAM23 (NM_003812.4) in a patient with drug-resistant, MRI-negative focal epilepsy accompanied by additional neurocognitive and behavioral issues. The ADAM23 variant was inherited from an unaffected parent. Notably, the same individual carried inherited, truncating variants in two other brain-expressed, loss-of-function-intolerant genes: TNRC6A and MAPK8IP3. CONCLUSION: These findings suggest that ADAM23 contributes to epilepsy with reduced penetrance, potentially influenced by oligogenic factors. Although descriptive and hypothesis-generating, our data underscore the complexity of currently unexplored genetic contributions to epilepsy.
AU  - Krenn, M.*
AU  - Nenning, K.H.*
AU  - Aull-Watschinger, S.*
AU  - Pataraia, E.*
AU  - Wagner, M.
AU  - Zimprich, F.*
C1  - 75424
C2  - 58236
CY  - 32 Jamestown Rd, London Nw1 7by, England
SP  - 454-457
TI  - ADAM23 haploinsufficiency as a putative oligogenic contributor in an individual with focal epilepsy.
JO  - Seizure
VL  - 131
PB  - W B Saunders Co Ltd
PY  - 2025
SN  - 1059-1311
ER  - 

TY  - JOUR
AB  - OBJECTIVE: To further delineate the clinical and genetic spectrum of epileptic and neurodevelopmental conditions associated with variants in STX1B. METHODS: We screened our diagnostic in-house database (comprising >20,000 exome sequencing datasets) for pathogenic and likely pathogenic variants inSTX1B. The detected cases were phenotyped in detail, and the findings were compared to previously published case reports. RESULTS: We identified four unrelated individuals with pathogenic or likely pathogenic variants in STX1B (one missense and three loss-of-function variants). All patients displayed epileptic phenotypes, including epileptiform discharges on electroencephalography (without apparent seizures), developmental and epileptic encephalopathy and focal epilepsy. Three of the four patients had developmental delay. Febrile seizures occurred in two individuals. One patient with focal epilepsy underwent epilepsy surgery without lasting improvement. The neuropathological workup of brain tissue revealed a mild malformation of cortical development without alterations of cortical lamination or dysplastic neurons. CONCLUSIONS: Our findings confirm the wide clinical range ofSTX1B-related epileptic conditions and highlight the necessity of genetic testing prior to epilepsy surgery in cases with monogenic epilepsy. The identification of loss-of-function variants in very differently affected individuals suggests that no clear genotype-phenotype correlation can be established.
AU  - Krenn, M.*
AU  - Schloegl, M.*
AU  - Pataraia, E.*
AU  - Gelpi, E.*
AU  - Schröder, S.*
AU  - Rauscher, C.*
AU  - Mayr, J.A.*
AU  - Kotzot, D.*
AU  - Zimprich, F.*
AU  - Meitinger, T.*
AU  - Wagner, M.
C1  - 61441
C2  - 50250
CY  - 32 Jamestown Rd, London Nw1 7by, England
SP  - 25-29
TI  - Delineation of epileptic and neurodevelopmental phenotypes associated with variants in STX1B.
JO  - Seizure
VL  - 87
PB  - W B Saunders Co Ltd
PY  - 2021
SN  - 1059-1311
ER  -