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Title
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XYLT1 mutations in Desbuquois dysplasia type 2
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Author
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Abstract
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| Desbuquois dysplasia (DBQD) is a severe condition characterized by short stature, joint laxity, and advanced carpal ossification. Based on the presence of additional hand anomalies, we have previously distinguished DBQD type 1 and identified CANT1 (calcium activated nucleotidase 1) mutations as responsible for DBQD type 1. We report here the identification of five distinct homozygous xylosyltransferase 1 (XYLT1) mutations in seven DBQD type 2 subjects from six consanguineous families. Among the five mutations, four were expected to result in loss of function and a drastic reduction of XYLT1 cDNA level was demonstrated in two cultured individual fibroblasts. Because xylosyltransferase 1 (XT-I) catalyzes the very first step in proteoglycan (PG) biosynthesis, we further demonstrated in the two individual fibroblasts a significant reduction of cellular PG content. Our findings of XYLT1 mutations in DBQD type 2 further support a common physiological basis involving PG synthesis in the multiple dislocation group of disorders. This observation sheds light on the key role of the XT-I during the ossification process. |
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Language
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English
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Source (journal)
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The American journal of human genetics / American Society of Human Genetics [Bethesda, Md] - New York, N.Y., 1949, currens
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Publication
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New York, N.Y.
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2014
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ISSN
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0002-9297
[print]
1537-6605
[online]
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DOI
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10.1016/J.AJHG.2014.01.020
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Volume/pages
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94
:3
(2014)
, p. 405-414
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ISI
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000332611400014
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Full text (Publisher's DOI)
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