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

Paulien A Terhal; Paula van Dommelen; Martine Le Merrer; Andreas Zankl; Marleen E H Simon; Sarah F Smithson; Carlo Marcelis; Bronwyn Kerr; Esther Kinning; Sahar Mansour; Raoul C M Hennekam; Annemarie H van der Hout; Valerie Cormier-Daire; Allan M Lund; Linda Goodwin; André Mégarbané; Melissa Lees; Regina C Betz; Edward S Tobias; Paul Coucke; Geert R Mortier

doi:10.1002/ajmg.c.31332

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

Paulien A Terhal, Paula van Dommelen, Martine Le Merrer, Andreas Zankl, Marleen E H Simon, Sarah F Smithson, Carlo Marcelis, Bronwyn Kerr, Esther Kinning, Sahar Mansour, Raoul C M Hennekam, Annemarie H van der Hout, Valerie Cormier-Daire, Allan M Lund, Linda Goodwin, André Mégarbané, Melissa Lees, Regina C Betz, Edward S Tobias, Paul CouckeGeert R Mortier

20 Citations (Scopus)

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 138.2 cm 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.

Original language	English
Journal	American Journal of Medical Genetics. Part C: Seminars in Medical Genetics
Volume	160C
Issue number	3
Pages (from-to)	205-16
Number of pages	12
ISSN	1552-4868
DOIs	https://doi.org/10.1002/ajmg.c.31332
Publication status	Published - 15 Aug 2012

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Terhal, P. A., van Dommelen, P., Le Merrer, M., Zankl, A., Simon, M. E. H., Smithson, S. F., Marcelis, C., Kerr, B., Kinning, E., Mansour, S., Hennekam, R. C. M., van der Hout, A. H., Cormier-Daire, V., Lund, A. M., Goodwin, L., Mégarbané, A., Lees, M., Betz, R. C., Tobias, E. S., ... Mortier, G. 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), 205-16. https://doi.org/10.1002/ajmg.c.31332

Terhal, PA, van Dommelen, P, Le Merrer, M, Zankl, A, Simon, MEH, Smithson, SF, Marcelis, C, Kerr, B, Kinning, E, Mansour, S, Hennekam, RCM, van der Hout, AH, Cormier-Daire, V, Lund, AM, Goodwin, L, Mégarbané, A, Lees, M, Betz, RC, Tobias, ES, Coucke, P & Mortier, GR 2012, 'Mutation-based growth charts for SEDC and other COL2A1 related dysplasias', American Journal of Medical Genetics. Part C: Seminars in Medical Genetics, vol. 160C, no. 3, pp. 205-16. https://doi.org/10.1002/ajmg.c.31332

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title = "Mutation-based growth charts for SEDC and other COL2A1 related dysplasias",

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 138.2 cm 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.",

author = "Terhal, {Paulien A} and {van Dommelen}, Paula and {Le Merrer}, Martine and Andreas Zankl and Simon, {Marleen E H} and Smithson, {Sarah F} and Carlo Marcelis and Bronwyn Kerr and Esther Kinning and Sahar Mansour and Hennekam, {Raoul C M} and {van der Hout}, {Annemarie H} and Valerie Cormier-Daire and Lund, {Allan M} and Linda Goodwin and Andr{\'e} M{\'e}garban{\'e} and Melissa Lees and Betz, {Regina C} and Tobias, {Edward S} and Paul Coucke and Mortier, {Geert R}",

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T1 - Mutation-based growth charts for SEDC and other COL2A1 related dysplasias

AU - Terhal, Paulien A

AU - van Dommelen, Paula

AU - Le Merrer, Martine

AU - Zankl, Andreas

AU - Simon, Marleen E H

AU - Smithson, Sarah F

AU - Marcelis, Carlo

AU - Kerr, Bronwyn

AU - Kinning, Esther

AU - Mansour, Sahar

AU - Hennekam, Raoul C M

AU - van der Hout, Annemarie H

AU - Cormier-Daire, Valerie

AU - Lund, Allan M

AU - Goodwin, Linda

AU - Mégarbané, André

AU - Lees, Melissa

AU - Betz, Regina C

AU - Tobias, Edward S

AU - Coucke, Paul

AU - Mortier, Geert R

PY - 2012/8/15

Y1 - 2012/8/15

N2 - 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 138.2 cm 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.

AB - 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 138.2 cm 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.

U2 - 10.1002/ajmg.c.31332

DO - 10.1002/ajmg.c.31332

M3 - Journal article

C2 - 22791362

SN - 1552-4868

VL - 160C

SP - 205

EP - 216

JO - American Journal of Medical Genetics. Part C: Seminars in Medical Genetics

JF - American Journal of Medical Genetics. Part C: Seminars in Medical Genetics

IS - 3

ER -

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

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