biostudies-literatureUnknown10(2)El Sherif R<h4>Objectives</h4>Collagen VI-related myopathy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy, caused by genetic variants in <i>COL6A1</i>, <i>COL6A2</i>, and <i>COL6A3</i> genes. Our objective was to report a newly identified patient with the pathogenic variants restricted to a polyadenylation signal in the 3'-untranslated region, which have not been reported in hereditary muscle disease.<h4>Methods</h4>We performed clinicopathologic diagnosis and analysis using whole-genome and RNA sequencing.<h4>Results</h4>We report Ullrich congenital muscular dystrophy caused by a homozygous deletion, c.*198_*466del, which includes a polyadenylation signal in the canonical last exon of the <i>COL6A2</i> gene. The parents were consanguineously married and had the heterozygous variant, but they were completely asymptomatic. In the patient's muscles, collagen VI was deficient in the sarcolemma, but present in the interstitium, showing the pattern of sarcolemma-specific collagen VI deficiency rather than a pattern of complete deficiency despite the lack of a polyadenylation signal. The RNA sequencing of the patient's muscle showed that alternative last exons were raised in <i>COL6A2</i> transcript.<h4>Discussion</h4>Our case provides a valuable example of the mechanism of alternative splicing switches for polyadenylation selection.Neurology. Geneticse200137https://www.ebi.ac.uk/biostudies/studies/S-EPMC10965357biostudies-literatureSplicing Switching of Alternative Last Exons Due to a Deletion Including Canonical Polyadenylation Site in <i>COL6A2</i> Gene Causes Recessive UCMD.PMC10965357Noguchi SEl Sherif RAwaya TSaito YNishino IfalseSplicing Switching of Alternative Last Exons Due to a Deletion Including Canonical Polyadenylation Site in <i>COL6A2</i> Gene Causes Recessive UCMD.<h4>Objectives</h4>Collagen VI-related myopathy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy, caused by genetic variants in <i>COL6A1</i>, <i>COL6A2</i>, and <i>COL6A3</i> genes. Our objective was to report a newly identified patient with the pathogenic variants restricted to a polyadenylation signal in the 3'-untranslated region, which have not been reported in hereditary muscle disease.<h4>Methods</h4>We performed clinicopathologic diagnosis and analysis using whole-genome and RNA sequencing.<h4>Results</h4>We report Ullrich congenital muscular dystrophy caused by a homozygous deletion, c.*198_*466del, which includes a polyadenylation signal in the canonical last exon of the <i>COL6A2</i> gene. The parents were consanguineously married and had the heterozygous variant, but they were completely asymptomatic. In the patient's muscles, collagen VI was deficient in the sarcolemma, but present in the interstitium, showing the pattern of sarcolemma-specific collagen VI deficiency rather than a pattern of complete deficiency despite the lack of a polyadenylation signal. The RNA sequencing of the patient's muscle showed that alternative last exons were raised in <i>COL6A2</i> transcript.<h4>Discussion</h4>Our case provides a valuable example of the mechanism of alternative splicing switches for polyadenylation selection.2024-01-01T00:00:00Z2024 Apr2025-04-21T21:27:10.432Z2025-04-05T18:25:15.637ZS-EPMC109653573854496610.1212/NXG.0000000000200137