Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review

Jaberi-Elahi syndrome is an extremely rare genetic disease caused by pathogenic variants in GTPBP2. The core symptoms of this disease are intellectual disability, motor development delay, abnormal reflexes, skeletal abnormalities, and visual impairment. In this study, we describe a three-year-old girl with a novel homozygous variant in GTPBP2 and a phenotype overlapping with Jaberi-Elahi syndrome. This variant (NM_019096.5:c.1289T > C, p.Leu430Pro) was identified by Whole Exome Sequencing and confirmed by Sanger sequencing although remains classified as VUS based on ACMG criteria. The proband demonstrated motor and intellectual developmental delay, muscle weakness, language disorder, facial dysmorphism, and poor growth. Hitherto, twenty-seven individuals with Jaberi-Elahi syndrome have been reported in the literature. This study, describes a review of the symptoms related to the Jaberi-Elahi syndrome. A large numbers of patients manifest motor development delay (26/28), sparse hair (26/28), and speech disorder (24/28). Moreover, a significant fraction of patients suffer from intellectual disability (23/28), hypotonia (23/28), skeletal problems (23/28), and visual impairment (18/28). In spite of previous patients, the proband in this study did not exhibit any skeletal abnormalities. In summary, we present evidence implicating a novel missense variant in Jaberi-Elahi syndrome, expanding and refining the genetic spectrum of this condition.