Mutation-based growth charts for SEDC and other COL2A1 related dysplasias

Terhal, Paulien A., van Dommelen, Paula, Le Merrer, Martine, Zankl, Andreas, Simon, Marleen E. H., Smithson, Sarah F., Marcelis, Carlo, Kerr, Bronwyn, Kinning, Esther, Mansour, Sahar, Hennekam, Raoul C. M., van der Hout, Annemarie H., Cormier-Daire, Valerie, Lund, Allan M., Goodwin, Linda, Megarbane, Andre, Lees, Melissa, Betz, Regina C., Tobias, Edward S., Coucke, Paul and Mortier, Geert R. (2012) Mutation-based growth charts for SEDC and other COL2A1 related dysplasias. American Journal of Medical Genetics Part C-Seminars in Medical Genetics, 160C 3: 205-216. doi:10.1002/ajmg.c.31332


Author Terhal, Paulien A.
van Dommelen, Paula
Le Merrer, Martine
Zankl, Andreas
Simon, Marleen E. H.
Smithson, Sarah F.
Marcelis, Carlo
Kerr, Bronwyn
Kinning, Esther
Mansour, Sahar
Hennekam, Raoul C. M.
van der Hout, Annemarie H.
Cormier-Daire, Valerie
Lund, Allan M.
Goodwin, Linda
Megarbane, Andre
Lees, Melissa
Betz, Regina C.
Tobias, Edward S.
Coucke, Paul
Mortier, Geert R.
Title Mutation-based growth charts for SEDC and other COL2A1 related dysplasias
Journal name American Journal of Medical Genetics Part C-Seminars in Medical Genetics   Check publisher's open access policy
ISSN 1552-4868
1552-4876
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1002/ajmg.c.31332
Volume 160C
Issue 3
Start page 205
End page 216
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2013
Language eng
Abstract From data collected via a large international collaborative study, we have constructed a growth chart for patients with molecularly confirmed congenital spondylo-epiphyseal dysplasia (SEDC) and other COL2A1 related dysplasias. The growth chart is based on longitudinal height measurements of 79 patients with glycine substitutions in the triple-helical domain of COL2A1. In addition, measurements of 27 patients with other molecular defects, such as arginine to cysteine substitutions, splice mutations, and mutations in the C-terminal propeptide have been plotted on the chart. Height of the patients progressively deviate from that of normal children: compared to normal WHO charts, the mean length/height is -2.6 SD at birth, -4.2 SD at 5 years, and -5.8 SD in adulthood. The mean adult height (male and female combined) of patients with glycine substitutions in the triple-helical region is 138.2cm but there is a large variation. Patients with glycine to cysteine substitutions tend to cluster within the upper part of the chart, while patients with glycine to serine or valine substitutions are situated between +1 SD and -1 SD. Patients with carboxy-terminal glycine substitutions tend to be shorter than patients with amino-terminal substitutions, while patients with splice mutations are relatively tall. However, there are exceptions and specific mutations can have a strong or a relatively mild negative effect on growth. The observation of significant difference in adult height between affected members of the same family indicates that height remains a multifactorial trait even in the presence of a mutation with a strong dominant effect.
Keyword Growth
Col2a1
Spondylo-epiphyseal dysplasia congenita
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 12 July 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
 
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