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Open Access Research article

Novel mutations in natriuretic peptide receptor-2 gene underlie acromesomelic dysplasia, type maroteaux

Saadullah Khan1, Raja Hussain Ali1, Sanaullah Abbasi1, Muhammad Nawaz1, Noor Muhammad2 and Wasim Ahmad1*

Author Affiliations

1 Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan

2 Department of Biotechnology & Genetic Engineering, Kohat University of Science & Technology (KUST), Kohat, Pakistan

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BMC Medical Genetics 2012, 13:44  doi:10.1186/1471-2350-13-44

Published: 12 June 2012

Abstract

Background

Natriuretic peptides (NPs) are peptide hormones that exert their biological actions by binding to three types of cell surface natriuretic peptide receptors (NPRs). The receptor NPR-B binding C-type natriuretic peptide (CNP) acts locally as a paracrine and/or autocrine regulator in a wide variety of tissues. Mutations in the gene NPR2 have been shown to cause acromesomelic dysplasia-type Maroteaux (AMDM), an autosomal recessive skeletal disproportionate dwarfism disorder in humans.

Methods

In the study, presented here, genotyping of six consanguineous families of Pakistani origin with AMDM was carried out using polymorphic microsatellite markers, which are closely linked to the gene NPR2 on chromosome 9p21-p12. To screen for mutations in the gene NPR2, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the families and sequenced.

Results

Sequence analysis of the gene NPR2 identified a novel missence mutation (p.T907M) in five families, and a splice donor site mutation c.2986 + 2 T > G in the other family.

Conclusion

We have described two novel mutations in the gene NPR2. The presence of the same mutation (p.T907M) and haplotype in five families (A, B, C, D, E) is suggestive of a founder effect.

Keywords:
Acromesomelic dysplasia-type Maroteaux; gene NPR2; missence mutation (T907M); splice site mutation c.2986 + 2 T > G