Compound heterozygosity in GPR56 with bilateral frontoparietal polymicrogyria

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Polymicrogyria is a congenital brain malformation characterized by excessive cortical folding.
• Bilateral frontoparietal polymicrogyria (BFPP) is a specific subtype of polymicrogyria linked to mutations in the GPR56 gene.
• BFPP is an autosomal recessive disorder affecting cortical lamination.

Observation:

• A Japanese female patient presented with severe developmental delays, epilepsy (Lennox-Gastaut syndrome), exotropia, and distinct brain abnormalities on MRI.
• Brain imaging revealed bilateral polymicrogyria with relative sparing of the perisylvian region and patchy white matter changes.
• The patient exhibited pontine hypoplasia, a less common finding in BFPP.

Findings:

• Compound heterozygous mutations (c.107G>A [p.S36N] and c.113G>A [p.R38Q]) in the GPR56 gene were identified in the patient.
• These mutations are located in the ligand-binding domain of the extracellular N-terminus of the GPR56 protein.
• This is the first report of compound heterozygous GPR56 mutations causing BFPP.

Implications:

• The findings expand the known spectrum of GPR56 mutations associated with BFPP.
• The specific mutation pattern may influence the phenotypic presentation, including the degree of perisylvian involvement and epilepsy type.
• This research contributes to understanding the genetic basis of human brain malformations and could inform future genetic diagnostics.