Clinico-radiological characteristics of two patients with geroderma osteodysplasticum caused by new nucleotide variants in the GORAB gene

Abstract

Geroderma osteodysplasticum (OMIM #231070) is a rare autosomal recessive disorder characterized by congenital wrinkled skin on the dorsal surface of the limbs and abdomen; marked osteoporosis in childhood. Pathogenic variants of the nucleotide sequence in the GORAB gene, which encodes the GORAB protein located in the Golgi apparatus and plays a crucial role in vesicle transport in the Golgi complex, lead to the disease. This is the first report of 2 patients with this disease in Russia. A detailed description of the clinical-radiological and genetic characteristics of these patients with new nucleotide variants in the GORAB gene in a compound heterozygous state is presented: c.170C>G (p.Ser57Ter) and c.790G>C (p.Ala264Pro); c.295C>T (p.Gln99Ter) and heterozygous deletion on chromosome 1 (chr1:g.170531967–170539494del), affecting exons 1 and 2 of the gene. The main clinical manifestations of the syndrome were congenital wrinkled skin, sagging cheeks, hypoplasia of the cheekbones, prognathism, muscle hypotonia and joint hypermobility. Radiological signs included congenital bilateral dislocation of the hip, compression fractures of the vertebral bodies, and disruption of the continuity of the growth plate of the distal femur and proximal tibia, referred to as “insertion.” The rarity of the syndrome, as well as the similarity of clinical manifestations with a heterogeneous group of hereditary diseases accompanied by decreased skin elasticity, leads to a late correct diagnosis. This necessitates the description of the clinical-genetic characteristics of the disease, the study of the dynamics of the formation of its phenotypic manifestations, and the methods of molecular-genetic diagnostics.