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. 1997 Jan;60(1):48–56.

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.

J Heikkinen 1, T Toppinen 1, H Yeowell 1, T Krieg 1, B Steinmann 1, K I Kivirikko 1, R Myllylä 1
PMCID: PMC1712545  PMID: 8981946

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.

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