Title
A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl hydroxylase activity in an ehlers-danlos VIA patient
Author
Walker, L.C.
Overstreet, M.A.
Siddiqui, A.
de Paepe, A.
Ceylaner, G.
Malfait, F.
Symoens, S.
Atsawasuwan, P.
Yamauchi, M.
Ceylaner, S.
Bank, R.A.
Yeowell, H.N.
TNO Preventie en Gezondheid
Publication year
2005
Abstract
The clinical diagnosis of a patient with the phenotype of Ehlers-Danlos syndrome type VI was confirmed biochemically by the severely diminished level of lysyl hydroxylase (LH) activity in the patient's skin fibroblasts. A novel homozygous mutation, a single base change of T1360 → G in exon 13 of the LH1 gene, predicted to result in W446G, was identified in the patient's full-length cDNA. This was confirmed in genomic DNA from both the patient and her parents, who were heterozygous for the mutation. This mutation was introduced into an LH1-pAcGP67 baculoviral construct and expressed, in parallel with normal LH1, in an insect cell system. The loss of LH activity in the mutated recombinant construct confirmed the pathogenicity of this mutation. Although not in the major catalytic site, this mutation occurs in a highly conserved region of the LH1 gene and may contribute to loss of activity by interfering with normal folding of the enzyme. Copyright © 2005 by The Society for Investigative Dermatology, Inc. Chemicals / CAS: procollagen lysine 2 oxoglutarate 5 dioxygenase, 9059-25-0; lysyl hydroxylase 1, human, EC 1.14.11.4; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase, EC 1.14.11.4
Subject
Collagen cross-linking
Collagen disorders
Collagen hydroxylation
Human skin fibroblasts
Mutation analysis
complementary DNA
genomic DNA
Anamnesis
Baculovirus expression system
Case report
Cross linking
DNA determination
Ehlers Danlos syndrome
Enzyme active site
Enzyme activity
Gene expression
Gene mutation
Heterozygosity
Homozygosity
Joint laxity
Kyphoscoliosis
Mutational analysis
Phenotype
Preschool child
Protein folding
Skin fibroblast
Child, Preschool
Ehlers-Danlos Syndrome
Female
Humans
Mutation
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
Structure-Activity Relationship
To reference this document use:
http://resolver.tudelft.nl/uuid:7001d01f-623a-40e9-bbf2-31f7022699d5
DOI
https://doi.org/10.1111/j.0022-202x.2005.23727.x
TNO identifier
238478
ISSN
0022-202X
Source
Journal of Investigative Dermatology, 124 (5), 914-918
Document type
article