Mutation-based growth charts for SEDC and other COL2A1 related dysplasias.
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.
Department of Biomedical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands. p.a.terhal@umcutrecht.nl
Paulien A
PA
Terhal
Paula
P
van Dommelen
Martine
M
Le Merrer
Andreas
A
Zankl
Marleen E H
ME
Simon
Sarah F
SF
Smithson
Carlo
C
Marcelis
Bronwyn
B
Kerr
Esther
E
Kinning
Sahar
S
Mansour
Raoul C M
RC
Hennekam
Annemarie H
AH
van der Hout
Valerie
V
Cormier-Daire
Allan M
AM
Lund
Linda
L
Goodwin
André
A
Mégarbané
Melissa
M
Lees
Regina C
RC
Betz
Edward S
ES
Tobias
Paul
P
Coucke
Geert R
GR
Mortier
D019943:Amino Acid Substitution / Q000235:genetics; D001827:Body Height / Q000235:genetics; D002648:Child; D003062:Codon / Q000235:genetics; D024043:Collagen Type II / Q000737:chemistry / Q000235:genetics*; D005260:Female; D057238:Growth Charts; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D017433:Protein Structure, Secondary; D012326:RNA Splicing / Q000235:genetics; D011859:Radiography; D055815:Young Adult
C499177:COL2A1 protein, human; D003062:Codon; D024043:Collagen Type II