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Title
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Mutation-based growth charts for SEDC and other **COL2A1** related dysplasias
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Author
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Abstract
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| 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. (C) 2012 Wiley Periodicals, Inc. |
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Language
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English
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Source (journal)
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American journal of medical genetics: part C: seminars in medical genetics. - Bognor Regis
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Publication
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Bognor Regis
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2012
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ISSN
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1552-4868
[print]
1552-4876
[online]
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DOI
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10.1002/AJMG.C.31332
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Volume/pages
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160
:3
(2012)
, p. 205-216
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ISI
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000306668500007
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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