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A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene.

Publication ,  Journal Article
Ha, VT; Marshall, MK; Elsas, LJ; Pinnell, SR; Yeowell, HN
Published in: J Clin Invest
April 1994

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.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

April 1994

Volume

93

Issue

4

Start / End Page

1716 / 1721

Location

United States

Related Subject Headings

  • Restriction Mapping
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • Mutation
  • Molecular Sequence Data
  • Male
  • Immunology
  • Humans
  • Heterozygote
  • Female
  • Ehlers-Danlos Syndrome
 

Citation

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Ha, V. T., Marshall, M. K., Elsas, L. J., Pinnell, S. R., & Yeowell, H. N. (1994). A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. J Clin Invest, 93(4), 1716–1721. https://doi.org/10.1172/JCI117155
Ha, V. T., M. K. Marshall, L. J. Elsas, S. R. Pinnell, and H. N. Yeowell. “A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene.J Clin Invest 93, no. 4 (April 1994): 1716–21. https://doi.org/10.1172/JCI117155.
Ha VT, Marshall MK, Elsas LJ, Pinnell SR, Yeowell HN. A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. J Clin Invest. 1994 Apr;93(4):1716–21.
Ha, V. T., et al. “A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene.J Clin Invest, vol. 93, no. 4, Apr. 1994, pp. 1716–21. Pubmed, doi:10.1172/JCI117155.
Ha VT, Marshall MK, Elsas LJ, Pinnell SR, Yeowell HN. A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. J Clin Invest. 1994 Apr;93(4):1716–1721.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

April 1994

Volume

93

Issue

4

Start / End Page

1716 / 1721

Location

United States

Related Subject Headings

  • Restriction Mapping
  • Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
  • Mutation
  • Molecular Sequence Data
  • Male
  • Immunology
  • Humans
  • Heterozygote
  • Female
  • Ehlers-Danlos Syndrome