1. Duplication of seven exons in the lysyl hydroxylase gene is associated with longer forms of a repetitive sequence within the gene and is a common cause for the type VI variant of Ehlers-Danlos syndrome
- Author
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J, Heikkinen, T, Toppinen, H, Yeowell, T, Krieg, B, Steinmann, K I, Kivirikko, and R, Myllylä
- Subjects
Male ,Base Sequence ,Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase ,Molecular Sequence Data ,DNA ,Exons ,Polymerase Chain Reaction ,Gene Frequency ,Haplotypes ,Multigene Family ,Humans ,Ehlers-Danlos Syndrome ,Female ,Amino Acid Sequence ,Dinucleotide Repeats ,Alleles ,Cells, Cultured ,Research Article - Abstract
The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessively inherited connective tissue disorder which, in most families, is due to a deficiency in lysyl hydroxylase activity. We have recently characterized a homozygous duplication of 8.9 kb in the lysyl hydroxylase gene (PLOD) in two EDS VI families. The duplication is caused by a homologous recombination of Alu sequences in introns 9 and 16. Using PCR, we have analyzed 26 additional EDS VI families from various countries and found that 7 of them have this duplication. Our data has shown a frequency of 19.1% for this mutant allele among 35 EDS VI families studied by us so far. Our haplotype analysis shows a variation in the sequence of DNA region surrounding the duplication. There is an association between a particular allele size class, the long form, at the dinucleotide repeat within intron 16 and the duplication mutation in PLOD. Screening of a general population revealed one positive finding among 582 alleles tested. An abnormal sequence in exon 17 of the gene, which generated a stop codon in the exon sequence and aberrant mRNA processing, was responsible for the nonfunctionality of the other allele in one of the compound heterozygous patients.
- Published
- 1997