A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene.
Open Access
- 1 April 1994
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 93 (4), 1716-1721
- https://doi.org/10.1172/jci117155
Abstract
In the present study, we have isolated and sequenced the complementary DNAs of two mutant alleles for lysyl hydroxylase (LH) in fibroblasts from one patient (AT750) with Ehlers-Danlos syndrome type VI (EDS VI). We have identified a putative mutation in each allele which may be responsible for the patient's decreased LH (normalized to prolyl hydroxylase) activity (24% of normal). Intermediate levels of LH activity were measured in the patient's parents, who are clinically normal (father 52%; mother 86%). After the cloning of cDNAs and amplification by PCR, sequence analysis revealed two equally distributed populations of cDNAs for LH in the AT750 cell line. Each allele revealed different but significant changes from the normal sequence. In one allele (allele 1), the most striking change was a triple base deletion that would result in the loss of residue Glu532. The most significant difference in the other allele (allele 2) was a G-->A change which would produce a Gly678-->Arg codon change in a highly conserved region of the enzyme. Restriction analysis identified that allele 1 was inherited from the proband's mother and allele 2 from the father. This study represents the first example of compound heterozygosity for the LH gene in an EDS VI patient, and it appears that there is an additive effect of each mutant allele on clinical expression in this patient.Keywords
This publication has 25 references indexed in Scilit:
- A homozygous stop codon in the lysyl hydroxylase gene in two siblings with Ehlers–Danlos syndrome type VINature Genetics, 1992
- Isolation of lysyl hydroxylase, an enzyme of collagen synthesis, from chick embryos as a homogeneous proteinBiochemical Journal, 1980
- Ascorbate Action on Normal and Mutant Human Lysyl Hydroxylases from Cultured Dermal FibroblastsJournal of Investigative Dermatology, 1979
- Collagen GlycosyltransferasesPublished by Elsevier ,1979
- Inherited human collagen lysyl hydroxylase deficiency: Ascorbic acid responseThe Journal of Pediatrics, 1978
- DNA sequencing with chain-terminating inhibitorsProceedings of the National Academy of Sciences, 1977
- Abnormal properties of collagen lysyl hydroxylase from skin fibroblasts of siblings with hydroxylysine-deficient collagen.JCI Insight, 1976
- Ehlers-Danlos syndrome in two siblings with deficient lysyl hydroxylase activity in cultured skin fibroblasts but only mild hydroxylysine deficit in skin.1975
- Hydroxylysine-Deficient Skin Collagen in a Patient with a Form of the Ehlers-Danlos SyndromeJournal of Bone and Joint Surgery, 1974
- A Heritable Disorder of Connective TissueNew England Journal of Medicine, 1972