A COMPOUND HETEROZYGOTE PATIENT WITH EHLERS-DANLOS-SYNDROME TYPE-VI HAS A DELETION IN ONE ALLELE AND A SPLICING DEFECT IN THE OTHER ALLELE OF THE LYSYL HYDROXYLASE GENE

We report the first deletion mutation and the first splicing defect in the lysyl hydroxylase gene in a compound heterozygote patient with Eh lers Danlos syndrome type V1 with markedly reduced lysyl hydroxylase a ctivity. Northern analysis of the RNA isolated from skin fibroblasts o f the patient demon strated the presence of a truncated lysyl hydroxyl ase mRNA. PCR and sequence analysis confirmed the truncation and indic ated that the cells contain two types of shortened mRNAs, one lacking the sequences corresponding to exon 16 and the other lacking that corr esponding to exon 17 of the lysyl hydroxylase gene. Analysis of genomi c DNA revealed deletion of the penultimate adenosine from the 3' end o f intron 15 from one allele. This defect was probably responsible for the skipping of exon 16 sequences from the transcript. The other allel e, inherited from the mother, contains an Alu-Alu recombination with a deletion of about 3,000 nucleotides from the gene; this abnormality e xplains the lack of exon 17 sequences The identified mutations in exon 16 and exon 17 do not alter the reading frame of the transcripts. (C) 1998 Wiley-Liss, Inc.