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

TY - JOUR

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

N1 - Copyright © 2012 Wiley Periodicals, Inc.

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 -