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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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
  • Linda Goodwin
  • André Mégarbané
  • Melissa Lees
  • Regina C Betz
  • Edward S Tobias
  • Paul Coucke
  • Geert R Mortier
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.
OriginalsprogEngelsk
TidsskriftAmerican Journal of Medical Genetics. Part C: Seminars in Medical Genetics
Vol/bind160C
Udgave nummer3
Sider (fra-til)205-16
Antal sider12
ISSN1552-4868
DOI
StatusUdgivet - 2012

ID: 48516602