Characterization of a COL1A1 splicing defect in a case of Ehlers-Danlos syndrome type VII: Further evidence of molecular homogeneity

M. D'Alessio, F. Ramirez, B. D. Blumberg, M. K. Wirtz, V. H. Rao, M. D. Godfrey, D. W. Hollister

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29 Scopus citations

Abstract

A child affected by the type VII form of Ehlers-Danlos syndrome (EDS VII) was shown to have a heterozygous structural defect in the amino-terminus of pro-α1(I) collagen. As a result, type I procollagen trimers containing defective subunits are not converted to mature collagen molecules. To identify the cause of the protein abnormality, specifically primed cDNAs and genomic DNA were PCR amplified and sequenced. This analysis disclosed that the protein structural defect is caused by a single base substitution (A for G) at position -1 of the splice donor site of intron 6 of the pro-α1 (I) collagen gene (COL1A1). The affected allele produces (a) transcripts lacking exon 6 sequences and (b), in lesser amount, normally spliced transcripts. Furthermore, the rate of exon 6 skipping is temperature dependent, for it appears to decrease substantially when the patient's fibroblasts are incubated at 31°C. These findings are similar to those we previously reported for other unrelated EDS VII cases and, therefore, reemphasize the molecular homogeneity of this rare connective tissue disorder.

Original languageEnglish (US)
Pages (from-to)400-406
Number of pages7
JournalAmerican Journal of Human Genetics
Volume49
Issue number2
StatePublished - Dec 1 1991

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

D'Alessio, M., Ramirez, F., Blumberg, B. D., Wirtz, M. K., Rao, V. H., Godfrey, M. D., & Hollister, D. W. (1991). Characterization of a COL1A1 splicing defect in a case of Ehlers-Danlos syndrome type VII: Further evidence of molecular homogeneity. American Journal of Human Genetics, 49(2), 400-406.