Journal ArticleDOI
Relative stability of a minimal CTG repeat expansion in a large kindred with myotonic dystrophy
TLDR
A large DM family is identified in which multiple members had minimal CTG repeat expansions, and in which the number of CTG repeats remained in the minimally expanded range through at least three, and possibly four, generations.Abstract:
The genetic basis for myotonic dystrophy (DM) is a CTG trinucleotide repeat expansion. The number of CTG repeats commonly increases in affected individuals of successive generations, in association with anticipation. We identified a large DM family in which multiple members had minimal CTG repeat expansions, and in which the number of CTG repeats remained in the minimally expanded range through at least three, and possibly four, generations. This relative stability of minimal CTG repeat expansions may help to maintain the DM mutation in the population.read more
Citations
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Characteristics of intergenerational contractions of the CTG repeat in myotonic dystropy
T. Ashizawa,M. Anvret,U. Grandell,M. Baiget,A. M. Cobo,J. M. Barcelo,R. G. Korneluk,B. Dallapiccola,G. Novelli,R. G. Fenwick +9 more
TL;DR: In this article, the authors examined 1,489 myotonic dystropy (DM) parent-offspring pairs, of which 95 (6.4%) showed such contractions in peripheral blood leukocytes (PBL).
Journal ArticleDOI
Frequency and stability of the myotonic dystrophy type 1 premutation
TL;DR: Data indicate that premutation alleles cannot be the long-term source of new DM1 families, which must ultimately arise from mutations of alleles within the upper normal size range.
Book ChapterDOI
Myotonic dystrophy types 1 and 2
Tetsuo Ashizawa,Partha S. Sarkar +1 more
TL;DR: Strong evidence supports the hypothesis that sequestration of muscle-blind like (MBNL) proteins by these expanded repeats leads to misregulated splicing of many gene transcripts in corroboration with the raised level of CUG-binding protein 1.
Journal ArticleDOI
Very Large (CAG)n DNA Repeat Expansions in the Sperm of Two Spinocerebellar Ataxia Type 7 Males
Darren G. Monckton,Maria L. Cayuela,Fiona K. Gould,Graham J. R. Brock,Rajith de Silva,Tetsuo Ashizawa +5 more
TL;DR: It is demonstrated directly by single molecule analyses that the expanded repeat of SCA7 is extraordinarily unstable in the male germline and biased toward massive increases.
Journal ArticleDOI
Epidemiology of myotonic dystrophy in Italy: re‐apprisal after genetic diagnosis
Gabriele Siciliano,Maria Laura Manca,Massimo Gennarelli,Corrado Angelini,Anna Rocchi,Alfonso Iudice,Marta Miorin,M. L. Mostacciuolo +7 more
TL;DR: A minimum prevalence rate of 9.31×10−5 inhabitants was found, consistent with epidemiological rates worldwide, and more than two times as high as those of two previous studies conducted in the same areas during the era prior to molecular genetic testing.
References
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Journal ArticleDOI
Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member
J. David Brook,Mila E. McCurrach,H G Harley,Alan Buckler,Deanna M. Church,Hiroyuki Aburatani,Kent W. Hunter,Vincent P. Stanton,Jean Paul Thirion,Thomas J. Hudson,Robert L. Sohn,Boris V. Zemelman,Russell G. Snell,S A Rundle,Steve Crow,June Davies,Peggy Shelbourne,Jessica L. Buxton,Clare Jones,Vesa Juvonen,Keith J. Johnson,Peter S. Harper,D.J. Shaw,David E. Housman +23 more
TL;DR: Using positional cloning strategies, this work has identified a CTG triplet repeat that undergoes expansion in myotonic dystrophy patients and PCR analysis of the interval containing this repeat indicates that unaffected individuals have been 5 and 27 copies.
Journal ArticleDOI
An unstable triplet repeat in a gene related to myotonic muscular dystrophy.
Ying-Hui Fu,Antonio Pizzuti,Raymond G. Fenwick,Jonathan King,S. Rajnarayan,Patrick W. Dunne,J. Dubel,G. A. Nasser,Tetsuo Ashizawa,P. de Jong,Bé Wieringa,R. G. Korneluk,M. B. Perryman,Henry F. Epstein,C. Thomas Caskey +14 more
TL;DR: These studies suggest that the mutational mechanism leading to DM is triplet amplification, similar to that occurring in the fragile X syndrome.
Journal ArticleDOI
Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I
TL;DR: In this paper, a sequence analysis of the repeat from 126 chromosomes reveals an interrupted repeat configuration in 98% of the unexpanded alleles but a contiguous repeat (CAG)n configuration in 30 expanded alleles from seven SCA1 families.
Journal ArticleDOI
The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy.
TL;DR: The correlation between the degree of CTG amplification and age of onset in 109 DM gene carriers from 17 families is reported and parent-child and sib-sib comparisons provide a framework in which to incorporate DNA diagnostic studies when counselling subjects and families at risk for DM.
Journal ArticleDOI
Origin of the expansion mutation in myotonic dystrophy.
TL;DR: The results strongly suggest that the initial predisposing event of myotonic dystrophy consisted of a transition from a (CTG)5 allele to anallele with 19 to 30 repeats, which may constitute a reservoir for recurrent DM mutations.
Related Papers (5)
Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member
J. David Brook,Mila E. McCurrach,H G Harley,Alan Buckler,Deanna M. Church,Hiroyuki Aburatani,Kent W. Hunter,Vincent P. Stanton,Jean Paul Thirion,Thomas J. Hudson,Robert L. Sohn,Boris V. Zemelman,Russell G. Snell,S A Rundle,Steve Crow,June Davies,Peggy Shelbourne,Jessica L. Buxton,Clare Jones,Vesa Juvonen,Keith J. Johnson,Peter S. Harper,D.J. Shaw,David E. Housman +23 more