Unstable DNA sequence in myotonic dystrophy

Harley, H G; Rundle, S.A.; Reardon, W; Myring, J.; Crow, S; Harper, Peter S.; Shaw, Duncan; Brook, David

doi:10.1016/0140-6736(92)90729-m

Cited by 172 publications

(73 citation statements)

References 10 publications

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“…In PCR analysis, we detected smeared bands of mutant alleles in all DM patients analyzed. Our molecular data in CDM were consistent with the results of previous reports Mahadevan et al, 1992;Harley et al, 1992). reported characteristic relationships between CTG repeat mutations and clinical phenotypes in a Japanese population.…”

Section: Discussionsupporting

confidence: 92%

Detection of the CTG repeat expansion in congenital myotonic dystrophy

et al. 1997

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SummaryMyotonic dystrophy (DM) is caused by an abnormal expansion of an unstable CTG trinucleotide repeat in the 3" untranslated region of mRNA encoding a putative serine/threonine protein kinase. We analyzed 59 patients with DM (28 congenital DM families: 27 families with maternal transmission and 1 paternal transmission) and 27 normal control subjects to evaluate their CTG repeat size between DM patients and the normal controls, and to search for a correlation between the clinical characteristics of congenital DM (CDM) and CTG repeat expansions. Analysis was on the basis of the Southern blot and polymerase chain reaction (PCR) methods, and by direct sequencing of PCR amplified CTG repeats. Analysis of intergenerational differences in the CTG repeat size for mother-child pairs showed a positive correlation (y= 1.0384x+ 1265.2, rz=0.311). In addition to the strong parental bias, this group showed genetic anticipation. There was a significant correlation of the CTG repeat expansion with disease severity. The largest CTG repeat expansion (2,293 CTG repeats) on average belonged to the severe CDM group, and the smallest (129 CTG repeats) to the subclinical DM group. The mutant allele of an asymptomatic father in the paternally transmitted pedigree revealed 75 CTG repeats, demonstrating that he was a DM protomutation carrier.

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Section: Discussionsupporting

confidence: 92%

Detection of the CTG repeat expansion in congenital myotonic dystrophy

et al. 1997

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“…20,21 Despite the diversity and variable severity of its symptoms, our study demonstrates the feasibility of determining which aspects of the disease are most significant to affected individuals. This study fills an important gap in the present literature.…”

Section: Resultsmentioning

confidence: 99%

Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1)

Heatwole

Bode²,

Johnson³

et al. 2012

Neurology

172

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Objective: To determine the most critical symptoms in a national myotonic dystrophy type 1 (DM1) population and to identify the modifying factors that have the greatest effect on the severity of these symptoms. Methods:We performed a cross-sectional study of 278 adult patients with DM1 from the national registry of patients with DM1 between April and August 2010. We assessed the prevalence and relative significance of 221 critical DM1 symptoms and 14 disease themes. These symptoms and themes were chosen for evaluation based on prior interviews with patients with DM1. Responses were categorized by age, CTG repeat length, gender, and duration of symptoms.Results: Participants with DM1 provided symptom rating survey responses to address the relative frequency and importance of each DM1 symptom. The symptomatic themes with the highest prevalence in DM1 were problems with hands or arms (93.5%), fatigue (90.8%), myotonia (90.3%), and impaired sleep or daytime sleepiness (87.9%). Participants identified fatigue and limitations in mobility as the symptomatic themes that have the greatest effect on their lives. We found an association between age and the average prevalence of all themes (p Ͻ 0.01) and between CTG repeat length and the average effect of all symptomatic themes on participant lives (p Ͻ 0.01). Conclusions:There are a wide range of symptoms that significantly affect the lives of patients with DM1. These symptoms, some previously underrecognized, have varying levels of importance in the DM1 population and are nonlinearly dependent on patient age and CTG repeat length. Neurology Myotonic dystrophy type 1 (DM1) is a multisystem disorder caused by an unstable trinucleotide repeat expansion on chromosome 19q13.3 in the DMPK gene.1-3 The core features of DM1 are myotonia, weakness, and early-onset cataracts (Ͻ50 years of age). Along with these core features, patients commonly report symptoms related to cognition, gastrointestinal function, sleep, fatigue, mood, ability to swallow, vision, social relations, and physical function. 4 The effect of each symptom on health-related quality of life is unknown. Furthermore, given the multisystem manifestations of DM1, we hypothesize that there are additional underrecognized symptoms that are important to patients and have a critical effect on their health status.

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“…Statistical data on DM mutation are essential for genetic counseling. The characteristics of DM dynamic mutation have been reported in English (Harley et al, 1992b(Harley et al, , 1993, French (Lavedan et al, 1993), Spanish (Cobo et al, 1993), Canadian (Hunter et al, 1992Tsilfidis et aL, 1992;Barcelo et al, 1993). Australian (Mulley el al., 1993), and American people (Ashizawa et aL, , 1993(Ashizawa et aL, , 1994aRedman et al, 1993).…”

Section: Introductionmentioning

confidence: 94%

Characteristics of dynamic mutation in Japanese myotonic dystrophy

et al. 1994

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SummaryTo study the characteristics, if any, of unstable CTG repeat sequence in Japanese myotonic dystrophy (DM), we analyzed DNA from 351 at risk individuals (including affected and non-affected carriers and their descendants) from 105 families in Japan. A total of 93 DM families (196 affected and 116 unaffected individuals), including 84 DM parentchild pairs (44 father-child and 40 mother-child pairs), were examined, many of which had been previously tested by linkage analysis. We detected unstable CTG repeat mutations between 0.15 kb and 8.7 kb in size. The size of the mutation correlated with the age of onset of symptoms. There was a significant difference in DM allele size among the four groups (congenital, juvenile onset, classical, and minimal). Congenital DM had on average the largest repeat sizes. Comparison of parent-child pairs showed that most offspring had a larger repeat size than their parents, with only 2 of 84 showing a definite decrease in repeat size. The correlation coefficients for maternal and paternal transmission were 0.41 and 0.15, respectively. The parental age (maternal and paternal) did not correlate with intergenerational change of repeat. These observations are similar to those reported in Caucasians.

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Unstable DNA sequence in myotonic dystrophy

Cited by 172 publications

References 10 publications

Detection of the CTG repeat expansion in congenital myotonic dystrophy

Detection of the CTG repeat expansion in congenital myotonic dystrophy

Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1)

Characteristics of dynamic mutation in Japanese myotonic dystrophy

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