Print Email Facebook Twitter Mutation-based growth charts for SEDC and other COL2A1 related dysplasias Title Mutation-based growth charts for SEDC and other COL2A1 related dysplasias Author Terhal, P.A. van Dommelen, P. Le Merrer, M. Zankl, A. Simon, M.E. Smithson, S.F. Marcelis, C. Kerr, B. Kinning, E. Mansour, S. Hennekam, R.C. van der Hout, A.H. Cormier-Daire, V. Lund, A.M. Goodwin, L. Mégarbané, A. Lees, M. Betz, R.C. Tobias, E.S. Coucke, P. Mortier, G.R. Publication year 2012 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. © 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 Subject HumanLS - Life StyleBSS - Behavioural and Societal SciencesHealthy for LifeHealthHealthy LivingCOL2A1GrowthSpondylo-epiphyseal dysplasia congenitaarginineasparaginecysteineglycinevalineadultadulthoodamino acid substitutionamino terminal sequenceanthropometric parametersarticlecarboxy terminal sequencechildcodonCol2a1 genefemalegenegene mutationgrowth curvehumanmajor clinical studymalenucleotide sequencepreschool childpriority journalspondyloepiphyseal dysplasia To reference this document use: http://resolver.tudelft.nl/uuid:7a0508d9-ed55-45ec-b6bb-cb2ed6d2ee69 DOI https://doi.org/10.1002/ajmg.c.31332 TNO identifier 462855 ISSN 1552-4868 Source American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, 160 C (3), 205-216 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.