This film helps
Making sense of Snap25.
It is made and presented by Chiara Klöckner, Leipzig University.
SNAP25 is a gene located on the 20th Chromosome. SNAP25 is part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein complex which is involved in exocytotic release of neurotransmitters.
The gene SNAP25 provides the instruction for a protein that is located in synapses in the brain. Genetic variants in SNAP25 may impair the release of neurotransmitters and affect communication between neurons in the brain.
Genetic variants in SNAP25 usually occur de novo, which means that the genetic change newly occurred in the child.
The disorder is called SNAP25 Developmental and Epileptic Encephalopathy (SNAP25-DEE), because individuals with variants in SNAP25 often have variable degrees of developmental delay and difficult to treat seizures that can start early in life. The degree of intellectual disability and individual health needs varies greatly.
While some children have severe complications in early childhood, others in contrast show mild intellectual disability and rare or no seizures.
Seizures are a major symptom in children with SNAP25-DEE. The onset of seizures is mostly before the age of two years. However, the range of onset of seizures is broad, and has been observed between the first days of life and early adolescence.
A wide range of seizure types are reported that include focal seizures, focal to bilateral tonic-clonic seizures, generalized seizures, epileptic spasms, myoclonic seizures, atonic seizures, absence-like seizures and status epilepticus. Seizure frequency ranges between numerous daily events to single, isolated seizures.
The human DNA contains the construction plan for every single component in the body. This construction plan consists of 3 billion letters. Sometimes, one single letter changes by chance, and this can change the construction plan and thus the component it encodes for (the protein).
Every single one of us has many genetic variants. Most of those variants do not cause any symptoms. However, some variants that cause symptoms are de novo variants.
SNAP25 mutations are almost always de novo. This means that the mutation arises anew spontaneously, and is not inherited from the mother or father. Therefore, the risk of having another affected child is quite low (less than 1%). SNAP25 Missense variations account for the greatest share of mutations, while nonsense and splice donor variants have also been reported.
The majority of children with SNAP25-DEE show developmental delay and variable cognitive impairment that ranges between mild to profound. Many children also have low muscle tone or movement disorders such as ataxia (problems coordinating movements), dystonia (twisting and continual movements) or tremor (shaking movements).
Some people with SNAP25-DEE show signs of an autism spectrum disorder, vision problems or loss of brain volume. The degree of intellectual disability and individual health needs varies greatly.
The incidence of SNAP25-DEE is estimated to be about 0.1-1:100.000 live births (López-Rivera et al., Brain 2020, PMID: 32168371).
From the publication: "De novo variants in SNAP25 cause an early-onset
developmental and epileptic encephalopathy", by Klockner, Platzer et. al.