Homozygous sequence variants in the NPR2 gene underlying Acromesomelic dysplasia Maroteaux type (AMDM) in consanguineous families

Ann Hum Genet. 2015 Jul;79(4):238-44. doi: 10.1111/ahg.12116. Epub 2015 May 11.

Abstract

Acromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive skeletal disorder characterized by disproportionate short stature with shortening of the acromesomelic sections of the limbs. AMDM is caused by mutations in the NPR2 gene located on chromosome 9p21-p12. The gene encodes the natriuretic peptide receptor B (NPR-B) that acts as an endogenous receptor for C-type natriuretic peptide (CNP). Both CNP and NPR-B are considered as important regulators of longitudinal growth. The study presented here investigated three consanguineous families (A, B, C) segregating AMDM in an autosomal recessive manner. Linkage in the families was established to the NPR2 gene on chromosome 9p12-21. Sequence analysis of the gene revealed two novel missense variants (p.Arg601Ser; p.Arg749Trp) in two families and a previously reported splice site variant (c.2986+2T>G) in the third family.

Keywords: Acromesomelic dysplasia-type Maroteaux; NPR2 gene; consanguineous families; missense and splice site variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Diseases, Developmental / genetics*
  • Bone Diseases, Developmental / pathology
  • Bone Diseases, Developmental / physiopathology
  • Consanguinity*
  • DNA Mutational Analysis*
  • Female
  • Humans
  • Male
  • Mutation
  • Mutation, Missense
  • Pedigree
  • RNA Splicing
  • Receptors, Atrial Natriuretic Factor / genetics*

Substances

  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B

Supplementary concepts

  • Acromesomelic dysplasia, Maroteaux type