Molecular characterization of acromesomelic dysplasia type maroteaux: A homozygous nonsense mutation in NPR2

Abstract

Acromesomelic dysplasia, type Maroteaux (AMDM) is an autosomal recessive skeletal condition distinguish by uneven growth plates, spines, and limbs. People with Acromesomelic dysplasia are often much shorter than average and have disproportionately short arms and legs. We investigated the cause of autosomal recessive skeletal disorder in a consanguineous Pakistani family comprises of four affected individuals across two generations. By utilizing whole exome sequencing, we investigated a nonsense mutation in the exon 2 of NPR2 gene (c.844 C>T, p.Q282X) as the possible cause of the disease. The nonsense NPR2 gene mutation causes the premature termination of NPR2 protein, resulting in a shortened protein, missing a significant structural component. Segregation of NPR2 gene variant (c.844 C>T, p. Q282X) was confirmed by Sanger sequencing across the pedigree. Furthermore, bioinformatics analysis such as proteins secondary and 3D protein structures predictions were also carried out to assess their functional impact. The results of this study can help the clinicians in differential and better diagnosis, developing carrier screening and parental diagnosis tests for the studied family can also aid in our understanding for the pathophysiology of the disease caused by NPR2 mutations