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Cited by 370Connective tissue disorders researchProtease and Inhibitor MechanismsDermatological and Skeletal Disorders

Human Ehlers-Danlos Syndrome Type VII C and Bovine Dermatosparaxis Are Caused by Mutations in the Procollagen I N-Proteinase Gene

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Colige, Alain, Sieron, Aleksander L., Li, Shi-Wu, Schwarze, Ulrike, Petty, Elizabeth, Wertelecki, Wladimir, Wilcox, William, Krakow, Deborah +6 more·1999·The American Journal of Human Genetics
DOI 10.1086/302504PMC PMC1377929
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Abstract

Ehlers-Danlos syndrome (EDS) type VIIC is a recessively inherited connective-tissue disorder, characterized by extreme skin fragility, characteristic facies, joint laxity, droopy skin, umbilical hernia, and blue sclera. Like the animal model dermatosparaxis, EDS type VIIC results from the absence of activity of procollagen I N-proteinase (pNPI), the enzyme that excises the N-propeptide of type I and type II procollagens. The pNPI enzyme is a metalloproteinase containing properdin repeats and a cysteine-rich domain with similarities to the disintegrin domain of reprolysins. We used bovine cDNA to isolate human pNPI. The human enzyme exists in two forms: a long version similar to the bovine enzyme and a short version that contains the Zn++-binding catalytic site but lacks the entire C-terminal domain in which the properdin repeats are located. We have identified the mutations that cause EDS type VIIC in the six known affected human individuals and also in one strain of dermatosparactic calf. Five of the individuals with EDS type VIIC were homozygous for a C-->T transition that results in a premature termination codon, Q225X. Four of these five patients were homozygous at three downstream polymorphic sites. The sixth patient was homozygous for a different transition that results in a premature termination codon, W795X. In the dermatosparactic calf, the mutation is a 17-bp deletion that changes the reading frame of the message. These data provide direct evidence that EDS type VIIC and dermatosparaxis result from mutations in the pNPI gene.

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  • Dermatosparaxis EDS is caused by homozygous or compound heterozygous mutations in ADAMTS2, the gene encoding ADAMTS-2.

    “Dermatosparaxis EDS (dEDS) is caused by homozygous or compound heterozygous mutations in ADAMTS2, the gene that encodes ADAMTS-2.”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Colige et al., 1999

  • Mutations in ADAMTS2 result in decreased activity of ADAMTS-2, leading to defects in processing of type I procollagen to mature type I collagen.

    “The mutations result in decreased activity of ADAMTS-2, which leads to defects in processing of type I procollagen to mature type I collagen [Colige et al., 1999;Colige et al., 2004;Van Damme et al., 2016].”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Colige et al., 1999

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Authors
Colige, A., Sieron, A. L., Li, S.-W., Schwarze, U., Petty, E., Wertelecki, W., Wilcox, W., Krakow, D., Cohn, D. H., Reardon, W., Byers, P. H., Lapière, C. M., Prockop, D. J., & Nusgens, B. V.
Affiliations
  • University of Liège (BE)
  • University of Washington (US)
  • University of Michigan (US)
  • University of South Alabama (US)
  • University of California, Los Angeles (US)
  • Great Ormond Street Hospital (GB)
Corresponding author
Colige, Alain
ORCID
Venue
The American Journal of Human Genetics
Publisher
Elsevier BV
Published
1999-08
Volume
65
Issue
2
Pages
308-317
ISSN
0002-9297 (ISSN-L)
DOI
10.1086/302504
PMC
PMC1377929
OpenAlex
W2081172215
Cited by
370
References
36
Citations by year
2026: 6 · 2025: 7 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 12 · 2018: 14 · 2017: 13 · 2016: 13 · 2015: 16 · 2014: 8 · 2013: 21 · 2012: 12
FWCI
5.65
Type
journal article
Language
en
Open access
Licence
Locations
  • The American Journal of Human Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion)
Funders
  • National Institutes of Health (AR 21557, AR 39837, HD 22657)
  • Fonds De La Recherche Scientifique - FNRS (3.4529.95)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
Keywords
dermatosparaxis, genetic mutations, premature stop codon, connective tissue diseases, skin fragility, cysteine-rich domain, bovine model, cDNA cloning
MeSH terms
Amino Acid Sequence, Animals, Cattle, Cattle Diseases, Cells, Cultured, Cloning, Molecular, Disease Models, Animal, DNA Mutational Analysis, Ehlers-Danlos Syndrome, Fibroblasts, Genotype, Humans, Infant, Male, Molecular Sequence Data, Mutation, Procollagen N-Endopeptidase, RNA, Messenger, Alternative Splicing, Codon, Terminator

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