TMEM151A phenotypic spectrum includes paroxysmal kinesigenic dyskinesia with infantile convulsions

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Paroxysmal kinesigenic dyskinesia (PKD) is a neurological disorder characterized by brief, involuntary movements.
• Benign familial infantile convulsions (BFIC) are a type of epilepsy that typically begins in infancy.
• The genetic basis for some forms of PKD and BFIC remains incompletely understood.

Purpose of the Study:

• To investigate the genetic cause of paroxysmal kinesigenic dyskinesia (PKD) with comorbid benign familial infantile convulsions (BFIC) in a multi-generational family.
• To identify novel genetic variants associated with the PKD-PKD/IC-BFIC disease spectrum.

Main Methods:

• Whole exome sequencing was performed on affected family members.
• Co-segregation analysis was used to validate the identified genetic variant.
• Clinical phenotyping of affected individuals was conducted.

Main Results:

• A novel heterozygous variant, c.1085A>G, in the TMEM151A gene was identified in affected individuals.
• This variant co-segregated with the phenotype across three generations.
• One individual presented with a combined phenotype of PKD and BFIC (PKD/IC).

Conclusions:

• The TMEM151A gene is implicated in the pathogenesis of paroxysmal kinesigenic dyskinesia (PKD).
• The findings suggest TMEM151A variants may contribute to a broader disease spectrum including PKD with infantile convulsions (PKD/IC) and BFIC.
• This study expands the understanding of the genetic underpinnings of movement and seizure disorders.