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J Clin Endocrinol Metab. 2015 Feb;100(2):E355-9. doi: 10.1210/jc.2014-2814. Epub 2014 Nov 11.

C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

Author information

1
Nemours Children's Clinic (R.C.O.), Jacksonville, Florida 32207; University of Otago (T.C.R.P., E.A.E.), Christchurch 8011, New Zealand; Nemours/Alfred I. duPont Hospital for Children (W.G.M., A.L.D., C.D., M.B.B.), Wilmington, Delaware 19803; University Hospital Freiburg (B.Z.), 79106 Freiburg, Germany; Keio University School of Medicine (T.H.), Tokyo 108-8345, Japan; Nagoya University School of Medicine (H.K.), Nagoya 464-8601, Japan; and University of North Carolina (A.S.A.), Chapel Hill, North Carolina 27599-2100.

Abstract

CONTEXT:

C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway.

OBJECTIVE:

The purpose of this study was to determine whether these syndromes exhibit evidence of CNP resistance as reflected by increases in plasma CNP and its amino-terminal propeptide (NTproCNP).

DESIGN:

This was a prospective, observational study.

SUBJECTS:

Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM.

RESULTS:

Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P < .0005). NTproCNP levels correlated with height velocity. Levels were also elevated in adults with achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P < .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08) and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01).

CONCLUSIONS:

In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01541306.

PMID:
25387261
DOI:
10.1210/jc.2014-2814
[Indexed for MEDLINE]

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