Broadening the spectrum of loss-of-function Variants in NPR-C-related extreme tall stature

Context: Natriuretic peptide receptor-C (NPR-C, encoded by NPR3) belongs to a family of cell membrane-integral proteins implicated in various physiological processes, including longitudinal bone growth. NPR-C acts as a clearance receptor of natriuretic peptides, including C-type natriuretic peptide (CNP), that stimulate the cGMP-forming guanylyl cyclase-coupled receptors NPR-A and NPR-B. Pathogenic variants in CNP, NPR2, and NPR3 may cause a tall stature phenotype associated with macrodactyly of the halluces and epiphyseal dysplasia. Objective: Here we report on a boy with 2 novel biallelic inactivating variants of NPR3. Methods: History and clinical characteristics were collected. Biochemical indices of natriuretic peptide clearance and in vitro cellular localization of NPR-C were studied to investigate causality of the identified variants. Results: We identified 2 novel compound heterozygous NPR3 variants c.943G>A p.(Ala315Thr) and c.1294A>T p.(Ile432Phe) in a boy with tall stature and macrodactyly of the halluces. In silico analysis indicated decreased stability of NPR-C, presumably resulting in increased degradation or trafficking defects. Compared to other patients with NPR-C loss-of-function, the phenotype seemed to be milder: pseudo-epiphyses in hands and feet were absent, biochemical features were less severe, and there was some co-localization of p.(Ile432Phe) NPR-C with the cell membrane, as opposed to complete cytoplasmic retention. Conclusion: With this report on a boy with tall stature and macrodactyly of the halluces we further broaden the genotypic and phenotypic spectrum of NPR-C-related tall stature.Genetics of disease, diagnosis and treatmen

Broadening the Spectrum of Loss-of-Function Variants in NPR-C-Related Extreme Tall Stature

Context: Natriuretic peptide receptor-C (NPR-C, encoded by NPR3) belongs to a family of cell membrane-integral proteins implicated in various physiological processes, including longitudinal bone growth. NPR-C acts as a clearance receptor of natriuretic peptides, including C-type natriuretic peptide (CNP), that stimulate the cGMP-forming guanylyl cyclase-coupled receptors NPR-A and NPR-B. Pathogenic variants in CNP, NPR2, and NPR3 may cause a tall stature phenotype associated with macrodactyly of the halluces and epiphyseal dysplasia.Objective: Here we report on a boy with 2 novel biallelic inactivating variants of NPR3.Methods: History and clinical characteristics were collected. Biochemical indices of natriuretic peptide clearance and in vitro cellular localization of NPR-C were studied to investigate causality of the identified variants.Results: We identified 2 novel compound heterozygous NPR3 variants c.943G>A p.(Ala315Thr) and c.1294A>T p.(Ile432Phe) in a boy with tall stature and macrodactyly of the halluces. In silico analysis indicated decreased stability of NPR-C, presumably resulting in increased degradation or trafficking defects. Compared to other patients with NPR-C loss-of-function, the phenotype seemed to be milder: pseudo-epiphyses in hands and feet were absent, biochemical features were less severe, and there was some co-localization of p.(Ile432Phe) NPR-C with the cell membrane, as opposed to complete cytoplasmic retention.Conclusion: With this report on a boy with tall stature and macrodactyly of the halluces we further broaden the genotypic and phenotypic spectrum of NPR-C-related tall stature

Elevated CO2 effects on minerals in wheat grains (2002)

<p>The data show the effect of doubling CO2 concentrations on C, N, P, K, Ca, S, Mg, Fe, Zn and Mn in wheat grains (% change). The data are for</p> <p><br>Loladze (2002) Rising atmospheric CO2 and human nutrition: toward globally imbalanced plant stoichiometry? Trends in Ecology & Evolution (TREE) 17:457-461</p> <p><br>TREE opinion pieces did not allow to include supporting data at the time of publication. The data are published here to allow to reproduce any of the results of the study, Fig. 1 (wheat grain/yellow bars).</p> <p> </p