Maternal uniparental isodisomy in a patient with autosomal recessive spastic paraplegia type 20

Spastic paraplegia type 20 (SPG20), also known as Troyer syndrome, is a complex form of hereditary spastic paraplegia (HSP), caused by biallelic deleterious variants in the SPART gene. We performed whole-exome sequencing (WES) in a 10-year-old boy with spastic paraparesis, dyskinesia, intellectual disability, speech delay, congenital anomalies, white matter changes, and sensorimotor neuropathy. WES revealed a homozygous nonsense variant in exon 4 of SPART (Gln374Ter), which was found in a heterozygous state in the mother and absent in the father. Analysis of polymorphisms from WES data indicated maternal uniparental disomy (UPD) of chromosome 13, explaining the observed homozygosity. This case underscores the importance of parental segregation studies when homozygous variants are identified, as UPD significantly impacts genetic counseling and recurrence risk. It also highlights the value of bioinformatics tools in WES trio analysis to detect UPD, improving diagnostic precision in clinical settings.