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SETD1B

Gene product: SET Domain Containing 1B, Histone Lysine.

Protein function: It can mediate the methylation of histone H3 lysine 4 (H3K4) site, thereby playing a role in epigenetic regulation of gene transcription [1].

Phenotype: Intellectual developmental disorder with seizures and language delay (AD) (some of which may manifest as Epilepsy With Myoclonic Absences, Epilepsy With Eyelid Myoclonias（Jeavons Syndrome）, Lennox-Gastaut Syndrome, and Progressive Myoclonus Epilepsies) [2-5].

Mutation database: ClinVar.

Clinical research: PubMed (PMID: 34345025 (Genet Med. 2021)；39765123 (Eur J Paediatr Neurol. 2025))

Medication reminder: The choice of medication is mainly based on different epilepsy syndromes. So far, it has been reported that drugs such as valproate sodium, levetiracetam, lamotrigine, phenobarbital, and nitrazepam are effective in treating some patients, while some patients do not respond well to multiple drug treatments [3-10]. In addition, based on the types of epilepsy syndromes and seizures caused by the gene as a whole, it is best to avoid using narrow-spectrum sodium channel blockers (such as carbamazepine and oxcarbazepine), as they may worsen the condition (personal opinion, for reference only).

 

References:

  1. De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism. Hum Genet. 2018 Jan;137(1):95-104.
  2. SETD1B-associated neurodevelopmental disorder. J Med Genet. 2021 Mar;58(3):196-204.
  3. De novo variants in SETD1B cause intellectual disability, autism spectrum disorder, and epilepsy with myoclonic absences. Epilepsia Open. 2019 May 24;4(3):476-481.
  4. SETD1B variants associated with absence seizures. Eur J Paediatr Neurol. 2025 Jan:54:68-74.
  5. Epilepsy with eyelid myoclonia with atonic seizures and generalized paroxysmal fast activity: A novel electroclinical phenotype associated with SETD1B pathogenic variant. Epileptic Disord. 2024 Apr;26(2):250-253.
  6. Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome. Genet Med. 2021 Nov;23(11):2122-2137.
  7. A novel de novo frameshift variant in SETD1B causes epilepsy. J Hum Genet. 2019 Aug;64(8):821-827.
  8. SETD1B-associated neurodevelopmental disorder. J Med Genet. 2021 Mar;58(3):196-204.
  9. Mental retardation, seizures and language delay caused by new SETD1B mutations: Three case reports. World J Clin Cases. 2024 Jan 16;12(2):383-391.
  10. Phenotypic spectrum of SETD1B-related disorder: Myoclonic absence seizures and concurrent intellectual disability - Insights from two cases. Seizure. 2024 Jan:114:57-60.