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Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (type VIIC) and common polymorphisms in the ADAMTS2 gene

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Abstract
Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3-5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14-16 at the mRNA level. Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population.

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MLA
COLIGE, A, Lieve Nuytinck, I HAUSSER, et al. “Novel Types of Mutation Responsible for the Dermatosparactic Type of Ehlers-Danlos Syndrome (type VIIC) and Common Polymorphisms in the ADAMTS2 Gene.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 123.4 (2004): 656–663. Print.
APA
COLIGE, A., Nuytinck, L., HAUSSER, I., VAN ESSEN, A., THIRY, M., HERENS, C., ADES, L., et al. (2004). Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (type VIIC) and common polymorphisms in the ADAMTS2 gene. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 123(4), 656–663.
Chicago author-date
COLIGE, A, Lieve Nuytinck, I HAUSSER, AJ VAN ESSEN, M THIRY, C HERENS, LC ADES, et al. 2004. “Novel Types of Mutation Responsible for the Dermatosparactic Type of Ehlers-Danlos Syndrome (type VIIC) and Common Polymorphisms in the ADAMTS2 Gene.” Journal of Investigative Dermatology 123 (4): 656–663.
Chicago author-date (all authors)
COLIGE, A, Lieve Nuytinck, I HAUSSER, AJ VAN ESSEN, M THIRY, C HERENS, LC ADES, Fransiska Malfait, Anne De Paepe, P FRANCK, G WOLFF, JC OOSTERWIJK, JHS SMITT, CM LAPIERE, and BV NUSGENS. 2004. “Novel Types of Mutation Responsible for the Dermatosparactic Type of Ehlers-Danlos Syndrome (type VIIC) and Common Polymorphisms in the ADAMTS2 Gene.” Journal of Investigative Dermatology 123 (4): 656–663.
Vancouver
1.
COLIGE A, Nuytinck L, HAUSSER I, VAN ESSEN A, THIRY M, HERENS C, et al. Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (type VIIC) and common polymorphisms in the ADAMTS2 gene. JOURNAL OF INVESTIGATIVE DERMATOLOGY. BLACKWELL PUBLISHING INC; 2004;123(4):656–63.
IEEE
[1]
A. COLIGE et al., “Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (type VIIC) and common polymorphisms in the ADAMTS2 gene,” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 123, no. 4, pp. 656–663, 2004.
@article{297108,
  abstract     = {Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3-5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14-16 at the mRNA level. Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population.},
  author       = {COLIGE, A and Nuytinck, Lieve and HAUSSER, I and VAN ESSEN, AJ and THIRY, M and HERENS, C and ADES, LC and Malfait, Fransiska and De Paepe, Anne and FRANCK, P and WOLFF, G and OOSTERWIJK, JC and SMITT, JHS and LAPIERE, CM and NUSGENS, BV},
  issn         = {0022-202X},
  journal      = {JOURNAL OF INVESTIGATIVE DERMATOLOGY},
  language     = {eng},
  number       = {4},
  pages        = {656--663},
  publisher    = {BLACKWELL PUBLISHING INC},
  title        = {Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (type VIIC) and common polymorphisms in the ADAMTS2 gene},
  url          = {http://dx.doi.org/10.1111/j.0022-202X.2004.23406.x},
  volume       = {123},
  year         = {2004},
}

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