title: Homozygous sequence variants in the NPR2 gene underlying Acromesomelic dysplasia Maroteaux type (AMDM) in consanguineous families.
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.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
authors.lastname: Irfanullah
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Umair
authors.affiliation: Department of Biotechnology & Genetic Engineering, Kohat University of Science & Technology, Kohat, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Saadullah
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D012326:RNA Splicing; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B
keywords: Acromesomelic dysplasia-type Maroteaux; NPR2 gene; consanguineous families; missense and splice site variants