Acromesomelic Dysplasia, Maroteaux type
 
Acromesomelic dysplasia, Maroteaux type is an autosomal recessive skeletal disorder that affects the limbs and the spine. Acromesomelic dysplasias, as a group, disproportionately affect the middle and distal segments of the limbs (forearms, forelegs, hands, and feet). There are other types of acromesomelic dysplasias, such as Hunter-Thompson (AMDH) and Grebe (AMDG), which are clinically, radiographically, and genetically distinct from the Maroteaux type (AMDM). Newborns affected with AMDM generally have normal weights, lengths, and head circumferences, but can have short appearing limbs. Older children and adults are significantly shorter than their peers, generally of normal intelligence, and are not expected to have any additional medical complications outside of their skeletal changes.
Our group determined that mutations in the NPR2 gene cause AMDM. The NPR2 gene encodes the natriuretic peptide receptor B (NPR-B) protein, which is also called guanylate cyclase B (GC-B). The gene is located on chromosome 9, in the 9p13.3 region.
Natriuretic peptide receptor B is a protein that spans the cell membrane. Two NPR-B molecules dimerize to form an active receptor. On the exterior of the cell, the NPR-B receptor can bind C-type natriuretic peptide (CNP). Upon binding, a conformational change in the dimer occurs, causing the part of NPR-B that is located inside the cell to convert GTP to cGMP. cGMP is a small signaling molecule that goes on to affect other pathways.
We have identified 28 disease-causing mutations in the NPR2 gene, including missense mutations, nonsense mutations, frameshift mutations from insertions or deletions, and splice-site mutations. Some of the mutations are associated with certain ethnic backgrounds so we request this information to help us focus our search.
Although AMDM is an recessive condition, requiring that both copies of the gene be mutated, it appears that having a mutation in just one copy of the gene may affect long bone growth and therefore height. We are collecting height information from patients’ families to test this idea.
Recent publications from our lab:
Bartels CF, Bukulmez H, Padayatti P, Rhee DK, van Ravenswaaij-Arts C, Pauli RM, Mundlos S, Chitayat D, Shih L-Y, Al-Gazali LI, Kant S, Cole T, Morton J, Cormier-Daire V, Faivre L, Lees M, Kirk J, Mortier GR, Leroy J, Zabel B, Kim CA, Crow Y, Braverman NE, van den Akker F, Warman ML. 2004. Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux. Am J Hum Genet 75:27-34
If you are a patient, or have a patient, with AMDM interested in participating in our research, please contact us. For sample submission instructions, please click on how to submit samples.
If you are a patient or family member interested in communicating with other families, please email Dr Warman. Whenever new family members contact us, emails or phone numbers between consenting families will be exchanged. The Center for the Study of Genetic Bone and Joint Disorders does not monitor communications directly between families, and therefore cannot be responsible for the accuracy of information exchanged.
Additional information on AMDM can be obtained through Online Mendelian Inheritance in Man, a database catalogue of human genes and genetic disorders edited by Victor A. McKusick and colleagues.The OMIM number for this disorder is 602875.
|
