title: A nonsense codon of exon 14 reduces lysyl hydroxylase mRNA and leads to aberrant RNA splicing in a patient with Ehlers-Danlos syndrome type VI.
abstract: Ehlers-Danlos syndrome type VI (EDSVI) is an autosomal recessively inherited connective tissue disease, characterized by kyphoscoliosis, muscular hypotonia and ocular manifestations. The cause of the syndrome is a deficiency in the activity of lysyl hydroxylase (LH), one of the enzymes involved in the post-translational modification of collagens. We describe here an unusual compound heterozygote British patient with EDSVI. Our investigations indicate that a maternally inherited nonsense mutation (Y511X) in exon 14 of the LH gene (PLOD1) results in a reduction of the mRNA level as well as a skipping of exon 14 sequences in the mRNA that produces a protein shortened by 38 amino acids. The transcription of the other allele of the LH gene is considerably reduced from the normal for reasons that are not yet known. As a consequence, the LH activity of the skin fibroblasts of the patient is markedly reduced.
authors.affiliation: Department of Biochemistry, University of Oulu, Finland.
authors.forename: B
authors.initials: B
authors.lastname: Pousi
authors.forename: J
authors.initials: J
authors.lastname: Heikkinen
authors.forename: J
authors.initials: J
authors.lastname: Schröter
authors.forename: M
authors.initials: M
authors.lastname: Pope
authors.forename: R
authors.initials: R
authors.lastname: Myllylä
mesh_terms: D015139:Blotting, Southern; D018389:Codon, Nonsense / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D005347:Fibroblasts; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D006113:United Kingdom
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; C067043:endodeoxyribonuclease NheI; D015252:Deoxyribonucleases, Type II Site-Specific