Abstract
Background:
Heterozygous loss-of-function mutations in the natriuretic peptide receptor B gene (NPR2) are responsible for short stature in patients without a distinct phenotype. Some of these patients have been treated with recombinant human growth hormone (rhGH) therapy with a variable response.
Case presentation:
The proband was a healthy boy who presented at the age of 5.1 years with familial short stature (height SDS of −3.1). He had a prominent forehead, a depressed nasal bridge, centripetal fat distribution and a high-pitched voice resembling that of children with GH deficiency. His hormonal evaluation showed low insulin-like growth factor-1 (IGF-1) but a normal GH peak at a stimulation test. During the first year of rhGH treatment, his growth velocity increased from 3.4 to 10.4 cm/year (height SDS change of +1.1). At the last visit, he was 8.8 years old and still on treatment, his growth velocity was 6.4 cm/year and height SDS was −1.8.
Results:
We identified through exome sequencing a novel heterozygous loss-of-function NPR2 mutation (c.2905G>C; p.Val969Leu). Cells cotransfected with the p.Val969Leu mutant showed a significant decrease in cyclic guanosine monophosphate (cGMP) production compared to the wild type (WT), suggesting a dominant negative effect.
Conclusions:
This case reveals a novel heterozygous loss-of-function NPR2 mutation responsible for familial short stature and the good response of rhGH therapy in this patient.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by Grants 2013/03236–5 (to A.A.L.J.) and 2014/50137-5 (SELA – Laboratório de Sequenciamento em Larga Escala) from the São Paulo Research Foundation (FAPESP); Grant 304678/2012–0 (to A.A.L.J.) from the National Council for Scientific and Technological Development (CNPq); MINECO (SAF2012-30871; SAF2015-66831-R), and the Jose Igea Award by the Foundation of the Spanish Society of Pediatric Endocrinology (FSEEP) to K.E.H. A.H-O. was a recipient of a FPI PhD studentship from the Basque Country.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplemental Material:
The online version of this article (DOI: 10.1515/jpem-2016-0280) offers supplementary material, available to authorized users.
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