DYNC1H1 variants associated with infant-onset epilepsy without neurodevelopmental disorders
Wu-Chen Wu1, Xiao-Yu Liang2, Dong-Ming Zhang2
1Department of Neurology, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Institute of Neuroscience, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China.
Seizure
|October 30, 2023
Summary
DYNC1H1 gene variants are linked to infant-onset epilepsy, with different variant types correlating to epilepsy severity and neurodevelopmental outcomes. This research expands understanding of DYNC1H1
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Variants in the DYNC1H1 gene are associated with abnormal brain development and neuromuscular disorders, often including epilepsy.
- Understanding the specific role of DYNC1H1 in epilepsy is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the relationship between DYNC1H1 gene variants and epilepsy.
- To analyze genotype-phenotype correlations in patients with DYNC1H1 variants and epilepsy.
Main Methods:
- Whole-exome sequencing was performed on patients diagnosed with epilepsy.
- A systematic review of previously reported epilepsy-related DYNC1H1 variants was conducted to correlate genotypes with phenotypes.
Main Results:
- DYNC1H1 variants were identified in four infants with epilepsy, including two de novo and two biallelic cases.
- De novo missense variants in the stem/stalk domains were linked to refractory epilepsy, while biallelic variants in inter-domain regions correlated with milder epilepsy and better outcomes.
- One patient exhibited pachygyria and neurodevelopmental issues; the others had normal development. Variants were rare and predicted to be damaging.
Conclusions:
- DYNC1H1 variants are potentially associated with infant-onset epilepsy, even without neurodevelopmental disorders, broadening the known phenotypic spectrum.
- Genotype-phenotype correlations provide insights into the mechanisms driving diverse clinical presentations in DYNC1H1-related epilepsy.
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