Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Brinckmann, J; Açil, Y; Feshchenko, S; Katzer, E; Brenner, R; Kulozik, A; Kügler, S.
Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a novel point mutation (W612C).
Arch Dermatol Res. 1998; 290(4):181-186
Doi: 10.1007/s004030050287
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Buschmann Eva Elina
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- Abstract:
- Ehlers-Danlos syndrome type VI (EDS VI) is a rare autosomal recessively inherited disease of connective tissue. The characteristic symptoms are hyperflexibility of joints and hyperelasticity of skin together with marked scoliosis, ocular manifestations and involvement of the vascular system. The underlying biochemical defect in EDS VI is a deficiency in lysyl hydroxylase (PLOD) activity resulting from mutations in the PLOD gene causing a low hydroxylysine content in various tissues. We found that two out of three patients showed a recently described duplication of about 800 bp in their LH mRNA. In the third patient we identified a new point mutation (2036 G-->C) resulting in a substitution of tryptophan by cysteine in the highly conserved C-terminal region of the enzyme (W612C). In addition, this mutation destroys a restriction site of MwoI. Restriction analysis of the patient's cDNA with MwoI showed the sole occurrence of the mutated transcript, while one allele in his genomic DNA contained the MwoI restriction site. Restriction analysis of the genomic DNA of the unaffected parents displayed a heterozygous loss of the restriction site for MwoI in the mother while the DNA of the father appeared normal. Our study demonstrates that the new point mutation (W612C) in conjunction with a functionless allele, most probably a null allele, for the LH gene may explain the functional deficiencies seen in this patient.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Amino Acid Substitution -
- Base Sequence -
- Blotting, Northern -
- DNA - analysis
- DNA - genetics
- DNA Mutational Analysis -
- DNA, Complementary - chemistry
- Deoxyribonucleases, Type II Site-Specific - genetics
- Ehlers-Danlos Syndrome - enzymology
- Ehlers-Danlos Syndrome - genetics
- Female -
- Genome -
- Heterozygote -
- Humans -
- Male -
- Multigene Family - genetics
- Point Mutation - genetics
- Polymorphism, Single-Stranded Conformational -
- Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - deficiency
- Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase - genetics
- RNA, Messenger - analysis
- Find related publications in this database (Keywords)
- Ehlers-Danlos syndrome type VI
- mutation
- lysyl hydroxylase