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Its assembly is a complex multistep process and the vulnerability of the process is manifested in muscular diseases. Mutations in COL6A1, COL6A2, and COL6A3 lead to the severe Ullrich Congenital Muscular Dystrophy (UCMD) and a spectrum of disease of varying severity including the milder Bethlem muscular dystrophy. The recently identified dominant intronic mutation in COL6A1 (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <a:mi>c<\/a:mi>\n                        <a:mo>.<\/a:mo>\n                        <a:mn>930<\/a:mn>\n                        <a:mo>+<\/a:mo>\n                        <a:mn>189<\/a:mn>\n                        <a:mi>C<\/a:mi>\n                        <a:mo>&gt;<\/a:mo>\n                        <a:mi>T<\/a:mi>\n                     <\/a:math>\n                  <\/jats:inline-formula>) leads to the partial in-frame insertion of a pseudoexon between exon 11 and exon 12. The pseudoexon is translated into 24 amino acid residues in the N-terminal region of the triple helix and results in the interruption of the typical G-X-Y motif. This recurrent de novo mutation leads to UCMD with a severe progression within the first decade of life. Here, we demonstrate that a mutation-specific antibody detects the mutant chain colocalizing with wild type collagen VI in the endomysium in patient muscle. Surprisingly, in the cell culture of patient dermal fibroblasts, the mutant chain is secreted as a single \u03b1 chain, while in parallel, normal collagen VI tetramers are assembled with the wild-type \u03b11 chain. The mutant chain cannot be incorporated into collagen VI tetramers but forms large aggregates in the extracellular matrix that may retain the ability to interact with collagen VI and potentially with other molecules. Also, \u03b11 chain-deficient WI-26 VA4 cells transfected with the mutant \u03b11 chain do not assemble collagen VI tetramers but, instead, form aggregates. Interestingly, both the wild type and the mutant single \u03b11 chains form amorphous aggregates when expressed in HEK293 cells in the absence of \u03b12 and \u03b13 chains. The detection of aggregated, assembly incompetent, mutant collagen VI \u03b11 chains provides novel insights into the disease pathophysiology of UCMD patients with the COL6A1 (<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <c:mi>c<\/c:mi>\n                        <c:mo>.<\/c:mo>\n                        <c:mn>930<\/c:mn>\n                        <c:mo>+<\/c:mo>\n                        <c:mn>189<\/c:mn>\n                        <c:mi>C<\/c:mi>\n                        <c:mo>&gt;<\/c:mo>\n                        <c:mi>T<\/c:mi>\n                     <\/c:math>\n                  <\/jats:inline-formula>) mutation.<\/jats:p>","DOI":"10.1155\/2023\/6892763","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T19:50:08Z","timestamp":1694029808000},"page":"1-16","source":"Crossref","is-referenced-by-count":6,"title":["The UCMD-Causing COL6A1 (<a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                     <a:mi>c<\/a:mi>\n                     <a:mo>.<\/a:mo>\n                     <a:mn>930<\/a:mn>\n                     <a:mo>+<\/a:mo>\n                     <a:mn>189<\/a:mn>\n                     <a:mi>C<\/a:mi>\n                     <a:mo>&gt;<\/a:mo>\n                     <a:mi>T<\/a:mi>\n                  <\/a:math>) Intron Mutation Leads to the Secretion and Aggregation of Single Mutated Collagen VI \u03b11 Chains"],"prefix":"10.1155","volume":"2023","author":[{"given":"Carolin D.","family":"Freiburg","sequence":"first","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-9802","authenticated-orcid":true,"given":"Herimela","family":"Solomon-Degefa","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-9698","authenticated-orcid":true,"given":"Patrick","family":"Freiburg","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7018-515X","authenticated-orcid":true,"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[{"name":"Colzyx AB, Medicon Village, SE-223 81 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Bolduc","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-0085","authenticated-orcid":true,"given":"Pierpaolo","family":"Ala","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital NIHR Biomedical Research Centre, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-5232","authenticated-orcid":true,"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital NIHR Biomedical Research Centre, London, 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