Center for the Study of Genetic Skeletal Disorders
Acromesomelic Dysplasia, Maroteaux type
Acromesomelic dysplasia, Maroteaux type (AMDM) is an autosomal recessive skeletal disorder that affects skeletal growth.
Newborns affected with AMDM generally have normal weights, lengths, and head circumferences, but may have short appearing limbs. Older children and adults who have AMDM, are significantly shorter than their peers and, as best we are aware, not expected to have additional medical complications outside of those associated with altered skeletal growth.
We identified mutations in the gene NPR2 as the cause of AMDM. The NPR2 gene encodes the natriuretic peptide receptor B (NPR-B) protein, also called guanylate cyclase B (GC-B). NPR-B is expressed in many tissues, including cells in the growth plates of growing bones. NPR-B is activated by a small protein called CNP (C-type natriuretic peptide) and it, in turn, activates other proteins including PRGK2 (cyclic GMP dependent protein kinase 2).
NPR-B appears to be important for regulating the complex process of cell proliferation and differentiation during skeletal growth. Individuals without working copies of NPR-B have AMDM, while individuals who carry one non-working copy of NPR-B tend to be shorter than non-carriers. We predict that 10 million humans carry one non-working copy of NPR-B and among individuals who are less than the 1st centile in height, approximately 1-in-20 will be NPR2 mutation carriers.
We have established an international consortium of patients, clinicians and basic scientists to study AMDM. The goals of this consortium are to improve the diagnosis and treatment for persons affected with AMDM.
Pooling resources and sharing ideas is important for advancing our knowledge about AMDM. Even though 10 million people are NPR2 mutation carriers, only 3500 persons in the entire world are affected with AMDM.
Among the questions we want to answer are:
- Do individuals with AMDM have other health problems that their health care providers should be aware of?
- Do all individuals with AMDM have mutations in NPR2, or might mutations in other components of this signaling pathway, such as CNP or PRGK2) also affect skeletal growth in children and resemble AMDM?
- How does the NPR2 signaling pathway specifically control skeletal growth in humans?
- Can components of the NPR2 signaling pathway be measured in blood and provide an accurate assessment of a child's skeletal health.
|Interested in participating?|
We welcome individuals and families who are affected by AMDM to participate in our research by contacting us.
To improve our ability to diagnose AMDM, we are seeking blood samples from patients with AMDM and their unaffected relatives.
To better understand how NPR2 functions within the body, we are seeking skin fibroblasts and/or skeletal tissue that can be recovered from patients with AMDM at the time of a medically-indicated procedure.
Studying the consequences of AMDM at the cellular, biophysical, and protein levels may help in furthering the development of new therapeutic strategies.
Physicians seeking assistance in making a diagnosis of AMDM or other forms of skeletal dysplasia are also welcome to contact us.