Mutation-based growth charts for SEDC and other COL2A1 related dysplasias
van Dommelen, P.
Le Merrer, M.
van der Hout, A.H.
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. © 2012 Wiley Periodicals, Inc. Molecular Sequence Numbers: GENBANK: NM_001844; Chemicals/CAS: arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; asparagine, 70-47-3, 7006-34-0; cysteine, 4371-52-2, 52-89-1, 52-90-4; glycine, 56-40-6, 6000-43-7, 6000-44-8; valine, 7004-03-7, 72-18-4
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Healthy for Life
Spondylo-epiphyseal dysplasia congenita
amino acid substitution
amino terminal sequence
carboxy terminal sequence
major clinical study
American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, 160 C (3), 205-216