Hanley PC, Kanwar HS, Martineau C, et al. - Since biallelic loss-of-function mutations in NPR2 result in acromesomelic dysplasia Maroteaux type (AMDM; OMIM 602875), whereas heterozygous mutations may account for 2-6% of idiopathic short stature (ISS), researchers sought to explain the physical proportions and growth characteristics of an extended family with novel NPR2 mutations including members with AMDM, ISS, or normal stature. They conducted whole exome sequencing in two healthy parents and two children with AMDM. Both mutant atrial natriuretic peptide receptor B (ANPRB) proteins were normally expressed in HEK293T cells and showed dominant negative impacts on wild type ANPRB catalytic activity. Biallelic NPR2 mutations cause severe skeletal dysplasia (ADMD), while heterozygous mutations result in a subtler phenotype characterized by progressive short stature, which is characterized by increasing height loss potential with age.