Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenazi Jewish patients with Tarui disease
- PMID:7479776
- PMCID: PMC40788
- DOI: 10.1073/pnas.92.22.10322
Nonsense mutation in the phosphofructokinase muscle subunit gene associated with retention of intron 10 in one of the isolated transcripts in Ashkenazi Jewish patients with Tarui disease
Abstract
Mutations in the human phosphofructokinase muscle subunit gene (PFKM) are known to cause myopathy classified as glycogenosis type VII (Tarui disease). Previously described molecular defects include base substitutions altering encoded amino acids or resulting in abnormal splicing. We report a mutation resulting in phosphofructokinase deficiency in three patients from an Ashkenazi Jewish family. Using a reverse transcription PCR assay, PFKM subunit transcripts differing by length were detected in skeletal muscle tissue of all three affected subjects. In the longer transcript, an insertion of 252 nucleotides totally homologous to the structure of the 10th intron of the PFKM gene was found separating exon 10 from exon 11. In addition, two single base transitions were identified by direct sequencing: [exon 6; codon 95; CGA (Arg) to TGA (stop)] and [exon 7; codon 172; ACC (Thr) to ACT (Thr)] in either transcript. Single-stranded conformational polymorphism and restriction enzyme analyses confirmed the presence of these point substitutions in genomic DNA and strongly suggested homozygosity for the pathogenic allele. The nonsense mutation at codon 95 appeared solely responsible for the phenotype in these patients, further expanding genetic heterogeneity of Tarui disease. Transcripts with and without intron 10 arising from identical mutant alleles probably resulted from differential pre-mRNA processing and may represent a novel message from the PFKM gene.
Similar articles
- Glycogenosis type VII (Tarui disease) in a Swedish family: two novel mutations in muscle phosphofructokinase gene (PFK-M) resulting in intron retentions.Nichols RC, Rudolphi O, Ek B, Exelbert R, Plotz PH, Raben N.Nichols RC, et al.Am J Hum Genet. 1996 Jul;59(1):59-65.Am J Hum Genet. 1996.PMID:8659544Free PMC article.
- Common mutations in the phosphofructokinase-M gene in Ashkenazi Jewish patients with glycogenesis VII--and their population frequency.Sherman JB, Raben N, Nicastri C, Argov Z, Nakajima H, Adams EM, Eng CM, Cowan TM, Plotz PH.Sherman JB, et al.Am J Hum Genet. 1994 Aug;55(2):305-13.Am J Hum Genet. 1994.PMID:8037209Free PMC article.
- Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency.Tsujino S, Servidei S, Tonin P, Shanske S, Azan G, DiMauro S.Tsujino S, et al.Am J Hum Genet. 1994 May;54(5):812-9.Am J Hum Genet. 1994.PMID:7513946Free PMC article.
- Mutations in muscle phosphofructokinase gene.Raben N, Sherman JB.Raben N, et al.Hum Mutat. 1995;6(1):1-6. doi: 10.1002/humu.1380060102.Hum Mutat. 1995.PMID:7550225Review.
- [Molecular pathology and gene diagnosis of muscle glycogenosis].Suzuki Y.Suzuki Y.Nihon Rinsho. 1997 Dec;55(12):3302-6.Nihon Rinsho. 1997.PMID:9436455Review.Japanese.
Cited by
- The sarcomeric M-region: a molecular command center for diverse cellular processes.Hu LY, Ackermann MA, Kontrogianni-Konstantopoulos A.Hu LY, et al.Biomed Res Int. 2015;2015:714197. doi: 10.1155/2015/714197. Epub 2015 Apr 15.Biomed Res Int. 2015.PMID:25961035Free PMC article.Review.
- Glycogenosis type VII (Tarui disease) in a Swedish family: two novel mutations in muscle phosphofructokinase gene (PFK-M) resulting in intron retentions.Nichols RC, Rudolphi O, Ek B, Exelbert R, Plotz PH, Raben N.Nichols RC, et al.Am J Hum Genet. 1996 Jul;59(1):59-65.Am J Hum Genet. 1996.PMID:8659544Free PMC article.
- PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis.Zhou M, Sun X, Wang C, Wang F, Fang C, Hu Z.Zhou M, et al.Sci Rep. 2022 Jul 8;12(1):11684. doi: 10.1038/s41598-022-15743-0.Sci Rep. 2022.PMID:35804014Free PMC article.
- A genome-wide association study of early-onset breast cancer identifies PFKM as a novel breast cancer gene and supports a common genetic spectrum for breast cancer at any age.Ahsan H, Halpern J, Kibriya MG, Pierce BL, Tong L, Gamazon E, McGuire V, Felberg A, Shi J, Jasmine F, Roy S, Brutus R, Argos M, Melkonian S, Chang-Claude J, Andrulis I, Hopper JL, John EM, Malone K, Ursin G, Gammon MD, Thomas DC, Seminara D, Casey G, Knight JA, Southey MC, Giles GG, Santella RM, Lee E, Conti D, Duggan D, Gallinger S, Haile R, Jenkins M, Lindor NM, Newcomb P, Michailidou K, Apicella C, Park DJ, Peto J, Fletcher O, dos Santos Silva I, Lathrop M, Hunter DJ, Chanock SJ, Meindl A, Schmutzler RK, Müller-Myhsok B, Lochmann M, Beckmann L, Hein R, Makalic E, Schmidt DF, Bui QM, Stone J, Flesch-Janys D, Dahmen N, Nevanlinna H, Aittomäki K, Blomqvist C, Hall P, Czene K, Irwanto A, Liu J, Rahman N, Turnbull C; Familial Breast Cancer Study; Dunning AM, Pharoah P, Waisfisz Q, Meijers-Heijboer H, Uitterlinden AG, Rivadeneira F, Nicolae D, Easton DF, Cox NJ, Whittemore AS.Ahsan H, et al.Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):658-69. doi: 10.1158/1055-9965.EPI-13-0340. Epub 2014 Feb 3.Cancer Epidemiol Biomarkers Prev. 2014.PMID:24493630Free PMC article.
References
Publication types
MeSH terms
Substances
Associated data
- Actions
Related information
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials