title: A null-mutated lysyl hydroxylase gene in a compound heterozygote British patient with Ehlers-Danlos syndrome type VI.
abstract: A British patient with EDS VI had two novel null mutations in the lysyl hydroxylase gene, one nucleotide deletion in the acceptor splice site of intron 4 in one allele, and an insertion of a C nucleotide in exon 2 of the other allele. The abnormal alleles lead to a markedly decreased lysyl hydroxylase mRNA levels, the finding making the affected cells different from the normal cells. In addition to the mutation analysis, we have revealed many exon-deleted splicing variants for lysyl hydroxylase mRNA which were first discovered in the affected cells, but tracks of similarly spliced mRNA species are also found in the cytoplasm of normal human skin fibroblasts. The data suggest that the splicing machinery of the cell is leaky generating differently spliced transcripts in the cell but only in a small amounts.
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Heikkinen
authors.forename: B
authors.initials: B
authors.lastname: Pousi
authors.forename: M
authors.initials: M
authors.lastname: Pope
authors.forename: R
authors.initials: R
authors.lastname: Myllylä
mesh_terms: D017398:Alternative Splicing; D002478:Cells, Cultured; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology*; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase