Id |
Subject |
Object |
Predicate |
Lexical cue |
TextSentencer_T1 |
0-131 |
Sentence |
denotes |
Bethlem myopathy and engineered collagen VI triple helical deletions prevent intracellular multimer assembly and protein secretion. |
TextSentencer_T2 |
132-286 |
Sentence |
denotes |
Mutations in the genes that code for collagen VI subunits, COL6A1, COL6A2, and COL6A3, are the cause of the autosomal dominant disorder, Bethlem myopathy. |
TextSentencer_T3 |
287-476 |
Sentence |
denotes |
Although three different collagen VI structural mutations have previously been reported, the effect of these mutations on collagen VI assembly, structure, and function is currently unknown. |
TextSentencer_T4 |
477-689 |
Sentence |
denotes |
We have characterized a new Bethlem myopathy mutation that results in skipping of COL6A1 exon 14 during pre-mRNA splicing and the deletion of 18 amino acids from the triple helical domain of the alpha1(VI) chain. |
TextSentencer_T5 |
690-818 |
Sentence |
denotes |
Sequencing of genomic DNA identified a G to A transition in the +1 position of the splice donor site of intron 14 in one allele. |
TextSentencer_T6 |
819-1063 |
Sentence |
denotes |
The mutant alpha1(VI) chains associated intracellularly with alpha2(VI) and alpha3(VI) to form disulfide-bonded monomers, but further assembly into dimers and tetramers was prevented, and molecules containing the mutant chain were not secreted. |
TextSentencer_T7 |
1064-1162 |
Sentence |
denotes |
This triple helical deletion thus resulted in production of half the normal amount of collagen VI. |
TextSentencer_T8 |
1163-1404 |
Sentence |
denotes |
To further explore the biosynthetic consequences of collagen VI triple helical deletions, an alpha3(VI) cDNA expression construct containing a 202-amino acid deletion within the triple helix was produced and stably expressed in SaOS-2 cells. |
TextSentencer_T9 |
1405-1621 |
Sentence |
denotes |
The transfected mutant alpha3(VI) chains associated with endogenous alpha1(VI) and alpha2(VI) to form collagen VI monomers, but dimers and tetramers did not form and the mutant-containing molecules were not secreted. |
TextSentencer_T10 |
1622-1784 |
Sentence |
denotes |
Thus, deletions within the triple helical region of both the alpha1(VI) and alpha3(VI) chains can prevent intracellular dimer and tetramer assembly and secretion. |
TextSentencer_T11 |
1785-2007 |
Sentence |
denotes |
These results provide the first evidence of the biosynthetic consequences of structural collagen VI mutations and suggest that functional protein haploinsufficiency may be a common pathogenic mechanism in Bethlem myopathy. |
T1 |
0-131 |
Sentence |
denotes |
Bethlem myopathy and engineered collagen VI triple helical deletions prevent intracellular multimer assembly and protein secretion. |
T2 |
132-286 |
Sentence |
denotes |
Mutations in the genes that code for collagen VI subunits, COL6A1, COL6A2, and COL6A3, are the cause of the autosomal dominant disorder, Bethlem myopathy. |
T3 |
287-476 |
Sentence |
denotes |
Although three different collagen VI structural mutations have previously been reported, the effect of these mutations on collagen VI assembly, structure, and function is currently unknown. |
T4 |
477-689 |
Sentence |
denotes |
We have characterized a new Bethlem myopathy mutation that results in skipping of COL6A1 exon 14 during pre-mRNA splicing and the deletion of 18 amino acids from the triple helical domain of the alpha1(VI) chain. |
T5 |
690-818 |
Sentence |
denotes |
Sequencing of genomic DNA identified a G to A transition in the +1 position of the splice donor site of intron 14 in one allele. |
T6 |
819-1063 |
Sentence |
denotes |
The mutant alpha1(VI) chains associated intracellularly with alpha2(VI) and alpha3(VI) to form disulfide-bonded monomers, but further assembly into dimers and tetramers was prevented, and molecules containing the mutant chain were not secreted. |
T7 |
1064-1162 |
Sentence |
denotes |
This triple helical deletion thus resulted in production of half the normal amount of collagen VI. |
T8 |
1163-1404 |
Sentence |
denotes |
To further explore the biosynthetic consequences of collagen VI triple helical deletions, an alpha3(VI) cDNA expression construct containing a 202-amino acid deletion within the triple helix was produced and stably expressed in SaOS-2 cells. |
T9 |
1405-1621 |
Sentence |
denotes |
The transfected mutant alpha3(VI) chains associated with endogenous alpha1(VI) and alpha2(VI) to form collagen VI monomers, but dimers and tetramers did not form and the mutant-containing molecules were not secreted. |
T10 |
1622-1784 |
Sentence |
denotes |
Thus, deletions within the triple helical region of both the alpha1(VI) and alpha3(VI) chains can prevent intracellular dimer and tetramer assembly and secretion. |
T11 |
1785-2007 |
Sentence |
denotes |
These results provide the first evidence of the biosynthetic consequences of structural collagen VI mutations and suggest that functional protein haploinsufficiency may be a common pathogenic mechanism in Bethlem myopathy. |