Identification of a Homozygous PGM2L1 Variant in a Male Patient With Developmental Delay and Seizures.

backgroundPGM2L1 gene variants are associated with developmental delays, seizures, and various neurological and physical symptoms. This study aims to report the clinical features and genetic findings in a male patient with developmental delay, regression, and seizures.

methodsWhole-exome sequencing (WES) was performed on the patient to identify the genetic etiology of the patient. Sanger sequencing was used for variant confirmation. Clinical evaluations were conducted, including cerebrospinal fluid analysis, cranial MRI, EEG, and neurological assessments.

resultsThe patient is a 1-year-old male who presented with psychomotor delays and developed seizures and impaired consciousness at 1 year of age. Cranial MRI revealed bilateral frontotemporal subarachnoid widening. Developmental regression was observed shortly after the onset of seizures. The EEG results showed diffuse slow background activity and epileptiform discharges. WES identified a rare homozygous variant in the PGM2L1 gene (OMIM: 611,610, NM_173582.6: c.1673delC, p.Thr558Ilefs*19), which was inherited from both parents. Sanger sequencing confirmed the presence of the variant, and it was evaluated as a likely pathogenic variant according to American College of Medical Genetics and Genomics (ACMG) guidelines.

conclusionOur study was the second report of a PGM2L1 gene variant associated with early-onset developmental delay and seizures, further expanding the genetic spectrum of this disorder.