A Novel Homozygous Frameshift GTPBP2 Variant in Jaberi-Elahi Syndrome: First Case Report from Türkiye

Jaberi-Elahi syndrome is a rare autosomal recessive neurodevelopmental disorder caused by biallelic loss-of-function variants in GTPBP2, a gene involved in ribosome-associated quality control. The condition shows marked phenotypic heterogeneity, including microcephaly, hypotonia or spasticity, developmental delay, intellectual disability, movement disorders, epilepsy, and variable neuroimaging findings.

We report a 4-month-old female infant born to consanguineous parents, presenting with severe microcephaly, developmental delay, hypotonia, and craniofacial features. Additional findings included left-sided pes equinovarus, secundum atrial septal defect, and periventricular white matter abnormalities on brain magnetic resonance imaging (MRI). No overt ectodermal abnormalities were observed. Ophthalmological examination revealed no structural anomalies; however, detailed retinal evaluation and electroretinography could not be performed. During follow-up, the patient developed early-onset seizures requiring antiepileptic treatment. Exome sequencing identified a novel homozygous frameshift variant in GTPBP2 (c.1165_1166del; p.(Leu389GlufsTer26)), classified as likely pathogenic. This homozygous variant was absent in population databases, and segregation analysis confirmed parental heterozygosity. This represents the first reported case with Jaberi-Elahi syndrome from Turkey.

Jaberi-Elahi syndrome should be considered in infants with severe congenital microcephaly, developmental delay, seizures, and craniofacial features, particularly in the context of consanguinity and abnormal brain MRI. This report expands the molecular and clinical spectrum of Jaberi-Elahi syndrome.