New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1)

Ashizawa, Tetsuo; Gonzales, I.; Ohsawa, Nakaaki; Singer, Robert H.; Devillers, Martine; Balasubramanyam, Ashok; Cooper, Thomas A.; Khajavi, Mehrdad; Lia-Baldini, Anne-Sophie; Miller, Geoffrey; Philips, Anne V.; Timchenko, Lubov; Waring, James; Yamagata, Hidehisa; Barbet, J. P.; Klesert, Todd R.; Tapscott, Stephen J.; Roses, A. D.; Wagner, Milton L.; Baiget, Montserrat; Martorell, Loreto; Browne, Gillian Butler; Eymard, B.; Gourdon, Geneviève; Junien, Claudine; Seznec, Hervé; Carey, Nessa; Gosling, M.; Maire, Pascal; Gennarelli, Massimo; Sato, Shin; Ansved, Tor; Kvist, Ulrik; Eriksson, Maria; Furling, Denis; Chen, E. J.; Housman, David E.; Luciano, Brenda; Siciliano, Michael J.; Spring, N.; Shimizu, Miho; Eddy, E. M.; Morris, Glenn E.; Krahe, Ralf; Furuya, Hirokazu; Adelman, John P.; Pribnow, D.; Furutama, Daisuke; Mathieu, Jean; Jones, Demonica; Kinoshita, M.; Abbruzzese, Claudia; Sinden, Richard R.; Wells, Robert D.; Pearson, Christopher E.; Kobayashi, Takayoshi; Johansson, Åsa; Salvatori, Sergio; Perryman, Benjamin; Swanson, Maurice S.; Gould, Fiona K.; Harris, Sarah E.; Johnson, Keith; Mitchell, A. M.; Monckton, Darren G.; Winchester, Catherine; Antonini, Giovanni; Day, John W.; Liquori, Christina L.; Ranum, Laura P.W.; Westerlaken, J.H.A.M.; Wieringa, Bé; Griffith, Jack D.; Michalowski, Susan; Moore, Heather C.; Hamshere, Marion; Korade, Željka; Thornton, Charles A.; Jaeger, H; Lehmann, Florian; Moorman, J. Randall; Mounsey, J. Paul; Mahadevan, Mani S.

doi:10.1212/wnl.54.6.1218

Cited by 196 publications

(9 citation statements)

References 16 publications

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“…In total, 30 patients with a molecular diagnosis of DM1 were recruited from the Neuromuscular and Neurological Rare Diseases Centre at San Camillo Forlanini Hospital (Rome, Italy) and from the Institute of Neurology at the Fondazione Policlinico Universitario A. Gemelli, IRCCS (Rome, Italy). In order to exclude the presence of a major cognitive impairment or mental retardation, patients had to be all suffering from a childhood, juvenile, or adulthood form of DM, as classified by the International Myotonic Dystrophy Consortium (IDMC) nomenclature (20), and they had to report a Mini Mental State Examination score (21) above 26. In addition, all patients had to show a normal level of intelligence quotient and no impairment in the comprehension ability, (16), anosognosia, or failures in school achievement.…”

Section: Participantsmentioning

confidence: 99%

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

et al. 2020

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Aim: To investigate the cortical thickness in myotonic dystrophy type 1 (DM1) and its potential association with patients' genetic triplet expansion and social cognition deficits.Methods: Thirty patients with DM1 underwent the Social Cognition Battery Test and magnetic resonance imaging (MRI) scanning at 3 T. Twenty-five healthy subjects (HSs) were enrolled in the study to serve as a control group for structural MRI data. To assess changes in cortical thickness in DM1 patients, they were compared to HSs using a t-test model. Correlations were used to assess potential associations between genetic and clinical characteristics and social cognition performances in the patient group. Additionally, multiple regression models were used to explore associations between cortical thickness, CTG triplet expansion size, and scores obtained by DM1 patients on the Social Cognition Battery.Results: DM1 patients showed low performances in several subtests of the Social Cognition Battery. Specifically, they obtained pathological scores at Emotion Attribution Test (i.e., Sadness, Embarrassment, Happiness, and Anger) and at the Social Situations Test (i.e., recognition of normal situation, recognition of aberrant behavior). Significant negative correlations were found between CTG triplet expansion size and Embarrassment, and Severity of Aberrant Behavior. Similarly, a negative correlation was found between patients' MIRS scores and Sadness. DM1 patients compared to HSs showed reduced thickness in the right premotor cortex, angular gyrus, precuneus, and inferior parietal lobule. Significant associations were found between patients' CTG triplet expansion size and thickness in left postcentral gyrus and in the left primary somatosensory cortex, in the posterior cingulate cortex bilaterally, and in the right lingual gyrus. Finally, significant associations were found between cortical thickness and sadness in the superior temporal gyrus, the right precentral gyrus, the right angular gyrus, and the left medial frontal gyrus bilaterally. DM1 patients showed a negative correlation between cortical thickness in the bilateral precuneus and in the left lateral occipital cortex Serra et al. Social Cognition Deficits in DM1 Brains and performance at the Social Situations Test. Finally, DM1 patients showed a negative correlation between cortical thickness in the left precuneus and in the superior frontal gyrus and scores at the Moral Distinction Test.Discussion: The present study shows both cortical thickness changes in DM1 patients compared to controls and significant associations between cortical thickness and patients' social cognition performances. These data confirm the presence of widespread brain damages associated with cognitive impairment in DM1 patients.

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Section: Participantsmentioning

confidence: 99%

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

et al. 2020

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“…The genetic defect underlying DM1 is multiple CTG repeats in the 3' untranslated region of a gene (DM1) on the long arm of the chromosome: the analysis of the CTG repeat on chromosome 19q13 [ 2 ]. Neuropathological, neuroimaging, and neurophysiological studies have demonstrated a variety of abnormalities of the central nervous system (CNS) in DM1 patients [ 3 – 5 ]. Magnetic resonance imaging (MRI) has been widely used to evaluate DM1.…”

Section: Introductionmentioning

confidence: 99%

Cerebral ventriculomegaly in myotonic dystrophy type 1: normal pressure hydrocephalus-like appearances on magnetic resonance imaging

et al. 2021

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Background Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI. Methods One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used binominal logistic regression analyses. Results The z-Evans Index was significantly larger in the patients than in the controls (0.30 ± 0.05 vs. 0.24 ± 0.02; p < 0.01). The z-Evans Index was independently associated with the callosal angle (p < 0.01) and pathological brain atrophy (p < 0.01) but not with age, gender, CTG repeat numbers, or CS-EPVS. Of the 34 patients older than 49 years, 7 (20.6%) were considered to have DESH. Conclusions Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

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“…Upon transmission to offspring the repeat length may increase and lead to a more severe disease, a mechanism known as anticipation. The broad spectrum of clinical presentations of DM1 overlap extensively with those of other disorders; and molecular testing is essential for a definitive diagnosis 6 .…”

Section: Introductionmentioning

confidence: 99%

“…standard PCR followed by fragment length analysis and Southern blot analysis 7 . The standard PCR technique, although sufficient in detecting the lower range of CTG expansions, is not reliable in amplifying repeats of over ~150 CTG repeats) and may fail to detect larger expansions when smaller alleles are preferentially amplified (allelic dropout) 6 . Therefore, samples in which only one repeat length is detected by PCR must be further analyzed for the possible presence of an expanded allele 7 .…”

Section: Introductionmentioning

confidence: 99%

Robust and accurate detection and sizing of repeats within the DMPK gene using a novel TP-PCR test

Leferink

Wong²,

Cai³

et al. 2019

Sci Rep

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Myotonic dystrophy type 1 is a multisystem disorder caused by the expansion of a trinucleotide repeat in the DMPK gene. In this study we evaluated the performance of the FastDM1 TM DMPK sizing kit in myotonic dystrophy type 1 testing. This commercially available triplet repeat-primed PCR based kit was validated using reference and clinical samples. Based on testing with 19 reference samples, the assay yielded repeat sizes within three repeats from the consensus reference length, demonstrating an accuracy of 100%. Additionally, the assay generated consistent repeat size information with a concentration range of template-DNA, and upon repetition and reproduction (CV 0.36% to 0.41%). Clinical performance was established with 235 archived prenatal and postnatal clinical samples, yielding results of 100% sensitivity (95% CI, 97.29% to 100%) and 100% specificity (95% CI, 96.19% to 100%) in classifying the samples into the respective genotype groups of 5–35 (normal), 36–50 (non-pathogenic pre-expansion), 51–150 (unstable intermediate-sized pathogenic) or >150 (unstable pathogenic) CTG repeats, respectively. Furthermore, the assay identified interrupted repeat expansions in all samples known to have interruptions, and also identified interruptions in a subset of the clinical samples.

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New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1)

Cited by 196 publications

References 16 publications

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1

Cerebral ventriculomegaly in myotonic dystrophy type 1: normal pressure hydrocephalus-like appearances on magnetic resonance imaging

Robust and accurate detection and sizing of repeats within the DMPK gene using a novel TP-PCR test

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