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


CONCLUSIONS
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.
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
Saadullah
S
Khan
Raja Hussain
RH
Ali
Sanaullah
S
Abbasi
Muhammad
M
Nawaz
Noor
N
Muhammad
Wasim
W
Ahmad
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001848:Bone Diseases, Developmental / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D005091:Exons; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult; D000099242:Atrial Natriuretic Factor Receptor B
D022821:RNA Splice Sites; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B