caa a22 4500 397575335 CHVBK 20180308164854.0 cr unu---uuuuu 161202e199611 xx s 000 0 eng 10.1093/hmg/5.11.1733 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.11.1733 A Splice-Junction Mutation in the Region of COL5A1 that Codes for the Carboxyl Propeptide of Proα1(V) Chains Results in the Gravis Form of the Ehlers-Danlos Syndrome (Type I) [Elektronische Daten] [Richard J. Wenstrup, Gregory T. Langland, Marcia C. Willing, Vinita N. D'Souza, William G. Cole] Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: α1(V)2α2(V) or α1(V)α2(V)α3(V). We report that genomic polymorphisms at the proα1(V) gene (COL5A1) locus cosegregated with the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three generation family. Affected family members, who had classical features including joint hyperextensibility, fragile skin, and widened, atrophic scars, were heterozygous for a 4 bp deletion at positions from +3 to +6 of intron 65, which resulted in removal of exon 65 sequences from processed mRNAs. Since exon 65 encodes 78 residues of the carboxyl propeptide, the expected result of this mutation is reduced efficiency in incorporating mutant proα1(V) chains into type V collagen molecules and reduced type V collagen synthesis. These studies indicate that heterozygous mutations in COL5A1 can result in EDS type I. However, linkage studies in other EDS I families indicate the disorder is heterogeneous; linkage to both COL5A1 and COL5A2 was excluded in two other families with EDS I while a fourth family was concordant for linkage to COL5A1 (Z = 2.11; θ = 0.00). © 1996 Oxford University Press Wenstrup Richard J. Division of Human Genetics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA aut Langland Gregory T. Division of Human Genetics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA aut Willing Marcia C. Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, IA, USA aut D'Souza Vinita N. The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada aut Cole William G. The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada aut Human Molecular Genetics Oxford University Press 5/11(1996-11), 1733-1736 0964-6906 5:11<1733 1996 5 hmg https://doi.org/10.1093/hmg/5.11.1733 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.11.1733 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wenstrup Richard J. Division of Human Genetics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA aut NATIONALLICENCE 700 1- Langland Gregory T. Division of Human Genetics, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA aut NATIONALLICENCE 700 1- Willing Marcia C. Department of Pediatrics, College of Medicine, University of Iowa, Iowa City, IA, USA aut NATIONALLICENCE 700 1- D'Souza Vinita N. The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada aut NATIONALLICENCE 700 1- Cole William G. The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/11(1996-11), 1733-1736 0964-6906 5:11<1733 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford