DUPLICATION OF 7 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

The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessive ly inherited connective tissue disorder which, In most families, is du e to a deficiency in lysyl hydroxylase activity, We have recently char acterized a homozygous duplication of 8.9 kb in the lysyl hydroxylase gene (PLOD) in two EDS VI families. The duplication is caused by a hom ologous 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, ur data has shown a f requency of 19.1% for this mutant allele among 35 EDS VI families stud ied by ms so far, Our haplotype analysis shows a variation in the sequ ence of DNA region surrounding the duplication, There is an associatio n between a particular allele size class, the long form, at the dinucl eotide repeat within intron 16 and the duplication mutation in PLOD, S creening of a general population revealed one positive finding among 5 82 alleles tested, An abnormal sequence in exon 17 of the gene, which generated a stop codon in the exon sequence and aberrant mRNA processi ng, was responsible for time nonfunctionality of the other allele in o ne of the compound heterozygous patients.