[Developmental and epileptic encephalopathy produced by the ATP1A2 mutation].

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Developmental and epileptic encephalopathies (DEE) are severe early-onset epilepsy syndromes.
• The ATP1A2 gene is implicated in DEE98, a rare condition.
• Genetic variants in SPART can cause autosomal recessive spastic paraplegia type 20 (SPG20).

Purpose of the Study:

• To describe a case of DEE98 with an atypical presentation.
• To investigate the pathogenicity of novel SPART variants identified in the patient.
• To differentiate between DEE98 and potential co-occurring SPG20.

Main Methods:

• Clinical examination and neuroimaging (MRI).
• Whole exome sequencing (WES) and trio Sanger sequencing.
• mRNA level analysis to assess variant pathogenicity.

Main Results:

• A patient presented with microcephaly, severe developmental delay, and epilepsy, diagnosed as DEE98 due to a de novo ATP1A2 mutation.
• Two novel heterozygous SPART variants were identified, initially suspected to cause SPG20.
• mRNA analysis indicated that the SPART variants were not pathogenic, ruling out SPG20.

Conclusions:

• This case expands the phenotypic spectrum of DEE98, highlighting atypical presentations.
• The identified SPART variants were determined to be non-pathogenic, excluding SPG20 in this patient.
• Careful genetic analysis and functional studies are crucial for diagnosing complex neurological disorders.