Saqib Ishaq*, Obaid Habib, Raheel Tahir, Abdul Aziz, Shabir Ahmad Usmani, Naghma Gulfam, Muhammad Shadab Jahangir, Yasir Ali
Acromesomelic dysplasia maroteaux type is a severe skeletal disorder that is caused due to loss of function mutations in the NPR2 gene which leads to the dysfunction of the Natriuretic Peptide Receptor (NPR2). Skeletal growth in AMDM patients falls off sharply after birth causing abnormal growth plate and short misshapen bones in the extremities and carrier parents of AMDM children are shorter than average. This protein comprises four domains: The extracellular ligand-binding domain, carboxyl-terminal guanylyl cyclase catalytic domain, intracellular protein kinase homology domain, and single membrane-spanning region. The missence mutation occur in chromosome 9p13.q12 with accession ID: P20594, result amino acid changes at 907 of Threonine into Methionine. The aims of this study were to find out the underlined missense mutation p.T907M in Pakistani family effect with acromesomelic dysplasia, type maroteaux. In this study a missense mutation determines by in Pakistani family which cause acromesomelic dysplasia, type maroteaux. Whole exome sequencing identified by the missense mutation was carried out by the causative gene. Bioinformatics tools were used for confirmation of pathogenicity of the identified mutations. The novel missense mutations, c. 2720C>T; p.T907M in NPR2 gene were identified in Pakistani family, respectively. Whole exome sequencing confirmed co-segregation of the mutations with disease phenotypes in Pakistani family. In Silico analysis of the sequence variants confirmed their pathogenicity. The report of NPR2 gene mutations in Pakistani family, which support the frequent involvement of NPR2 sequence variants in acromesomelic dysplasia, type maroteaux.
Published Date: 2025-01-11; Received Date: 2023-09-15