eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
Current issue Archive Manuscripts accepted About the journal Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
3/2017
vol. 55
 
Share:
Share:
more
 
 
abstract:
Original paper

A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy – a case report and review of the genotype–phenotype correlation

Agnieszka A. Koppolu, Agnieszka Madej-Pilarczyk, Małgorzata Rydzanicz, Joanna Kosińska, Piotr Gasperowicz, Jolanta Dorszewska, Wojciech Kozubski, Barbara Steinborn, Andrzej M. Kochański, Rafał Płoski

Folia Neuropathol 2017; 55 (3): 214-220
Online publish date: 2017/09/30
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
Collagen VI-related myopathy is a group of disorders affecting skeletal muscles and connective tissue. The most common symptoms are muscle weakness and joint deformities which limit the movement and progress over time. Several forms of collagen VI-related myopathies have been described: Bethlem myopathy, an intermediate form and Ullrich congenital muscular dystrophy, which is the most severe. Here we report a novel de novo c.1056+3A>C substitution in intron 14 of the COL6A1 gene encoding alpha-chains of collagen VI in a 13-year-old girl suffering from collagen VI (ColVI) myopathy. Analysis performed on cDNA generated from the RNA obtained from the patient’s blood cells showed that the reported variant leads to the entire exon 14 skipping and probably results in an in-frame deletion of 18 amino acids of the COL6A1 protein. Clinical presentation, abnormal secretion of the collagen demonstrated in muscle biopsy and the COL6A1 c.1056+3A>C mutation justify classification of the presented case as ColVI myopathy with moderate-progressive course. Analysis of the literature indicates that the donor splice site of COL6A1 intron 14, associated with the phenotype of Bethlem myopathy or intermediate form, is a hot spot for ColVI myopathies.
keywords:

COL6A1, RNA splicing, Bethlem myopathy

references:
Arts WF, Bethlem J, Volkers WS. Further investigations on benign myopathy with autosomal dominant inheritance. J Neurol 1978; 217: 201-206.
Baker NL, Mörgelin M, Pace RA, Peat RA, Adams NE, Gardner RJ, Rowland LP, Miller G, De Jonghe P, Ceulemans B, Hannibal MC, Edwards M, Thompson EM, Jacobson R, Quinlivan RC, Aftimos S, Kornberg AJ, North KN, Bateman JF, Lamandé SR. Molecular consequences of dominant Bethlem myopathy collagen VI mutations. Ann Neurol 2007; 62: 390-405.
Bertini E, Pepe G. Collagen type VI and related disorders: Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Eur J Paediatr Neurol 2002; 6: 193-198.
Bethlem J, Wijngaarden GK. Benign myopathy, with autosomal dominant inheritance. A report on three pedigrees. Brain 1976; 99: 91-100.
Brinas L, Richard P, Quijano-Roy S, Gartioux C, Ledeuil C, Lacène E, Makri S, Ferreiro A, Maugenre S, Topaloglu H, Haliloglu G, Pénisson-Besnier I, Jeannet PY, Merlini L, Navarro C, Toutain A, Chaigne D, Desguerre I, de Die-Smulders C, Dunand M, Echenne B, Eymard B, Kuntzer T, Maincent K, Mayer M, Plessis G, Rivier F, Roelens F, Stojkovic T, Taratuto AL, Lubieniecki F, Monges S, Tranchant C, Viollet L, Romero NB, Estournet B, Guicheney P, Alla-mand V. Early onset collagen VI myopathies: Genetic and clinical correlations. Ann Neurol 2010; 68: 511-520.
Brunak S, Engelbrecht J, Knudsen S. Prediction of human mRNA donor and acceptor sites from the DNA sequence. J Mol Biol 1991; 220: 49-65.
Camacho Vanegas O, Bertini E, Zhang RZ, Petrini S, Minosse C, Sabatelli P, Giusti B, Chu ML, Pepe G. Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI. Proc Natl Acad Sci U S A 2001; 98: 7516-7521.
Desmet FO, Hamroun D, Lalande M, Collod-Béroud G, Claustres M, Béroud C. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 2009; 37: e67.
Foley AR, Quijano-Roy S, Collins J, Straub V, McCallum M, Deconinck N, Mercuri E, Pane M, D’Amico A, Bertini E, North K, Ryan MM, Richard P, Allamand V, Hicks D, Lamandé S, Hu Y, Gualandi F, Auh S, Muntoni F, Bönnemann CG. Natural history of pulmonary function in collagen VI-related myopathies. Brain 2013; 136: 3625-3633.
Jobsis GJ, Boers JM, Barth PG, de Visser M. Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures. Brain 1999; 122: 649-655.
Lamande SR, Shields KA, Kornberg AJ, Shield LK, Bateman JF. Bethlem myopathy and engineered collagen VI triple helical deletions prevent intracellular multimer assembly and protein secretion. J Biol Chem 1999; 274: 21817-21822.
Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, Marie SK, Chu ML, Swoboda K, Muntoni F, Bonnemann CG, Flanigan KM, Bushby KM, Weiss RB. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet 2005; 42: 108-120.
Okada M, Kawahara G, Noguchi S, Sugie K, Murayama K, Nonaka I, Hayashi YK, Nishino I. Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan. Neurology 2007; 69: 1035-1042.
Park HJ, Choi YC, Kim SM, Kim SH, Hong YB, Yoon BR, Chung KW, Choi BO. Molecular Genetic Diagnosis of a Bethlem Myopathy Family with an Autosomal-Dominant COL6A1 Mutation, as Evidenced by Exome Sequencing. J Clin Neurol 2015; 11: 183-187.
Pepe G, Giusti B, Bertini E, Brunelli T, Saitta B, Comeglio P, Bolognese A, Merlini L, Federici G, Abbate R, Chu ML. A heterozygous splice site mutation in COL6A1 leading to an in-frame deletion of the alpha1(VI) collagen chain in an italian family affected by bethlem myopathy. Biochem Biophys Res Commun 1999; 258: 802-807.
Reese MG, Eeckman FH, Kulp D, Haussler D. Improved splice site detection in Genie. J Comput Biol 1997; 4: 311-323.
Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, Mesirov JP. Integrative genomics viewer. Nat Biotechnol 2011; 29: 24-26.
Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 2013; 14: 178-192.
Ullrich O. Kongenitale, atonisch-sklerotische Muskeldystrophie, ein weiterer Typus der heredodegenerativen Erkrankungen des neuromuskulären Systems. Zeitschrift für die gesamte Neurologie und Psychiatrie 1930; 126: 171-201.
Wang M, Marin A. Characterization and prediction of alternative splice sites. Gene 2006; 366: 219-227.
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe