Сlinical and Radiological Characteristics of Two Patients with Acromesomelic Dysplasia Maroteaux Type with New Mutation in the NRP2 Gene

Relevance. Acromezomelic dysplasia Maroteaux type (AMDM) is a rare variant of autosomal recessive skeletal disorder. The disease is caused by mutations in the NPR2 gene, coding the protein product which is one of the main regulators of endochondral ossification. To date, 49 mutations in this gene have been identified, more than half of which are missense substitutions. The presence of polymorphism of phenotypic manifestations makes it necessary to describe the features of clinical and radiological characteristics of the disease in patients with newly identified mutations in the gene, which will help to optimize its diagnosis. Case presentation. The clinical and radiological characteristics of two siblings with newly identified mutations c.125_126insTGGCG (p.Trp42CysfsTer12) and (p.Arg767Ter) in the NPR2 gene are described. Intra-family polymorphism of clinical manifestations is shown. Discussion. Clinical manifestations and radiological data in two siblings with AMDM caused by new mutations in the NPR2 gene and analysis of the literature data allowed us to conclude that there is no correlation of the severity of clinical signs and the type of mutations in the gene. Patients are born with normal growth and weight, and clinical manifestations (disproportionate dwarfism) appeared during the first year of life. The main radiological signs are shortening of tubular bones, most pronounced in the upper limbs and wedge-shaped formation of the vertebral bodies. Genotype-phenotype correlations confirmed the hypothesis that the majority of mutations leading to the disease is localized within the ligand-binding and guanylate cyclase domains. Conclusion. The obvious genetic heterogeneity, the similarity of the clinical manifestations of individual nosological groups of skeletal dysplasias, as well as the presence of intrafamily and interfamily polymorphism of clinical manifestations allows us to consider sequencing of a clinical exome or whole exome as the optimal method for diagnosing this group of diseases.

acromezomelic dysplasia, NPR2 gene, exome sequencing