Description:
DYSTROPHIA MYOTONICA 1; DM1
DYSTROPHIA MYOTONICA PROTEIN KINASE; DMPK
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Muscular Dystrophies
GeT-RM Samples |
| Class |
Disorders of Connective Tissue, Muscle, and Bone |
| Class |
Disorders with Trinucleotide Expansions |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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Relation to Proband
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proband
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Confirmation
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Molecular characterization after cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
4.48 |
| Passage Frozen |
4 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| CTG TRINUCLEOTIDE REPEAT EXPANSION ANALYSIS |
Mutational analysis of DNA from this subject with myotonic dystrophy performed by Dr. Robert G. Korneluk, Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, Canada, showed that the CTG trinucleotide repeat expansion length was greater than or equal to 4.5 kb determined by Southern blot analysis. This corresponds to up to 2000 CTG repeats. |
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| Gene |
DMPK |
| Chromosomal Location |
19q13.2-q13.3 |
| Allelic Variant 1 |
605377.0001; MYOTONIC DYSTROPHY |
| Identified Mutation |
(CTG)n EXPANSION; The consistent genetic defect associated with myotonic dystrophy is an amplified trinucleotide CTG repeat in the 3-prime untranslated region of the serine-threonine kinase gene DMK on 19q. Unaffected individuals have between 5 and 27 copies. DM patients who are minimally affected have at least 50 repeats, while more severely affected patients have expansion of the repeat-containing segment up to several kilobases. |
| Remarks |
Bone deformities; muscle wasting and myotonia; one DMPK allele harbors approximately 1700 copies of the CTG trinucleotide repeat, as assayed by Southern analysis; the other DMPK allele is normal, with 5 copies of the CTG trinucleotide repeat, as detected by PCR. |
| Asano K, Yoshimi K, Takeshita K, Mitsuhashi S, Kochi Y, Hirano R, Tingyu Z, Ishida S, Mashimo T, CRISPR Diagnostics for Quantification and Rapid Diagnosis of Myotonic Dystrophy Type 1 Repeat Expansion Disorders ACS synthetic biology13:3926-3935 2024 |
| PubMed ID: 39565688 |
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| Neault N, O'Reilly S, Baig AT, Plaza-Diaz J, Azimi M, Farooq F, Baird SD, MacKenzie A, High-throughput kinome-RNAi screen identifies protein kinase R activator (PACT) as a novel genetic modifier of CUG foci integrity in myotonic dystrophy type 1 (DM1) PloS one16:e0256276 2020 |
| PubMed ID: 34520479 |
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| Leferink M, Wong DPW, Cai S, Yeo M, Ho J, Lian M, Kamsteeg EJ, Chong SS, Haer-Wigman L, Guan M, Robust and accurate detection and sizing of repeats within the DMPK gene using a novel TP-PCR test Scientific reports9:8280 2019 |
| PubMed ID: 31164682 |
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| Rafehi H, Szmulewicz DJ, Bennett MF, Sobreira NLM, Pope K, Smith KR, Gillies G, Diakumis P, Dolzhenko E, Eberle MA, Barcina MG, Breen DP, Chancellor AM, Cremer PD, Delatycki MB, Fogel BL, Hackett A, Halmagyi GM, Kapetanovic S, Lang A, Mossman S, Mu W, Patrikios P, Perlman SL, Rosemergy I, Storey E, Watson SRD, Wilson MA, Zee DS, Valle D, Amor DJ, Bahlo M, Lockhart PJ, Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS American journal of human genetics105:151-165 2019 |
| PubMed ID: 31230722 |
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| van der Bent ML, Paulino da Silva Filho O, Willemse M, Hällbrink M, Wansink DG, Brock R, The nuclear concentration required for antisense oligonucleotide activity in myotonic dystrophy cells FASEB journal : official publication of the Federation of American Societies for Experimental Biology105:fj201900263R 2019 |
| PubMed ID: 31311315 |
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| Tankard RM, Bennett MF, Degorski P, Delatycki MB, Lockhart PJ, Bahlo M, Detecting Expansions of Tandem Repeats in Cohorts Sequenced with Short-Read Sequencing Data American journal of human genetics105:fj201900263R 2017 |
| PubMed ID: 30503517 |
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| Kalman L, Tarleton J, Hitch M, Hegde M, Hjelm N, Berry-Kravis E, Zhou L, Hilbert JE, Luebbe EA, Moxley RT, Toji L, Development of a Genomic DNA Reference Material Panel for Myotonic Dystrophy Type 1 (DM1) Genetic Testing The Journal of molecular diagnostics : JMD105:fj201900263R 2012 |
| PubMed ID: 23680132 |
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| Ho TH, Savkur RS, Poulos MG, Mancini MA, Swanson MS, Cooper TA, Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy Journal of cell science118:2923-33 2005 |
| PubMed ID: 15961406 |
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| Savkur RS, Philips AV, Cooper TA, Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet29(1):40-7 2001 |
| PubMed ID: 11528389 |
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| Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA,
Swanson MS, Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with
myotonic dystrophy. EMBO J19(17):4439-48 2000 |
| PubMed ID: 10970838 |
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| Chen C, Hong YK, Ontiveros SD, Egholm M, Strauss WM, Single base discrimination of CENP-B repeats on mouse and human Chromosomes with PNA-FISH. Mamm Genome10:13-8 1999 |
| PubMed ID: 9892726 |
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| Michalowski S, Miller JW, Urbinati CR, Paliouras M, Swanson MS, Griffith J, Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein. Nucleic Acids Res27(17):3534-42 1999 |
| PubMed ID: 10446244 |
| Passage Frozen |
4 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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