Homozygous myotonic dystrophy: Clinical findings in two patients and review of the literature

Zühlke, Christine; Roeder, Elizabeth; Purmann, Sabine; Wieczorek, Dagmar; Curry, Cynthia J.; Loustalet, Cheri; Hellenbroich, Yorck; Richardt, Hans Helmut; Gillessen‐Kaesbach, Gabriele

doi:10.1002/ajmg.a.31772

Cited by 3 publications

(4 citation statements)

References 10 publications

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“…As DM1 is inherited in an autosomal dominant manner, our data do not conclusively show whether DMPK‐dependent β‐adrenergic alterations could be involved in the DM1 cardiac phenotype. However, although rare, some cases of homozygous DM1 have been reported, 18 and our results may offer important clues for understanding the molecular mechanisms contributing to their phenotype.…”

Section: Discussionmentioning

confidence: 65%

Altered β‐adrenergic response in mice lacking myotonic dystrophy protein kinase

et al. 2011

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The protein kinase product of the gene mutated in myotonic dystrophy 1 (DMPK) is reported to play a role in cardiac pathophysiology. To gain insight into the molecular mechanisms modulated by DMPK, we characterize the impact of DMPK ablation in the context of cardiac β-adrenergic function. Our data demonstrate that DMPK knock-out mice present altered β-agonist-induced responses and suggest that this is due, at least in part, to a reduced density of β1-adrenergic receptors in cardiac plasma membranes.

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Section: Discussionmentioning

confidence: 65%

Altered β‐adrenergic response in mice lacking myotonic dystrophy protein kinase

et al. 2011

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“…Of note, symptomatic variability is dependent on the age of exam. For instance, intellectual disability is not diagnosed until after school age and therefore cannot be assessed in our patients nor those discussed in Cerghet et al [] and Zuhlke et al [], both presumed to fall in the congenital DM1 category based on expansion length.…”

Section: Discussionmentioning

confidence: 91%

“…Most individuals with myotonic dystrophy type 1 are heterozygous, meaning only one allele has a CTG expansion of greater than 50 repeats. Twelve cases of homozygous DM1 have been reported to date [Cobo et al, ; Martorell et al, ; Akbas et al, ; Abbruzzese et al, ; Zuhlke et al, ; Cerghet et al, ]. Three of these individuals have one allele expansion that falls within the premutation range (35–49) and one that falls above the affected cutoff of 50 repeats.…”

Section: Introductionmentioning

confidence: 99%

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Two is better than one: A case of homozygous myotonic dystrophy type 1

Carroll

Quaid

Stone

et al. 2013

American J of Med Genetics Pt A

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Myotonic dystrophy type 1 is an autosomal dominant condition caused by a trinucleotide CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. The phenotypic features of myopathic facies, generalized weakness, and myotonia are thought to be dependent on repeat number, with larger expansions generally leading to earlier and/or more severe disease. The vast majority of individuals are heterozygous for an expanded allele and an allele in the normal range. In this clinical report, we describe two brothers with congenital myotonic dystrophy type 1. The younger of the two siblings is one of only 13 homozygous patients ever reported in the literature. He carries two expanded alleles: one with 1,170 repeats and the other with >100 repeats. We present his clinical picture in relation to his more severely affected heterozygous brother as well as other published homozygous cases. Finally, we discuss the inconsistency between repeat size and symptomatic expression as it applies to the current proposed mechanisms of myotonic dystrophy type 1 pathogenicity.

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Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus

Cleary

Tomé

Castel

et al. 2010

Nat Struct Mol Biol

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Myotonic dystrophy, caused by DM1 CTG/CAG repeat expansions, shows varying instability levels between tissues and across ages within patients. We determined DNA replication profiles at the DM1 locus in patient fibroblasts and tissues from DM1 transgenic mice of various ages showing different instability. In patient cells, the repeat is flanked by two replication origins demarcated by CTCF sites, with replication diminished at the expansion. In mice, the expansion replicated from only the downstream origin (CAG as lagging template). In testes from mice of three different ages, replication toward the repeat paused at the earliest age and was relieved at later ages-coinciding with increased instability. Brain, pancreas and thymus replication varied with CpG methylation at DM1 CTCF sites. CTCF sites between progressing forks and repeats reduced replication depending on chromatin. Thus, varying replication progression may affect tissue- and age-specific repeat instability.

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Homozygous myotonic dystrophy: Clinical findings in two patients and review of the literature

Cited by 3 publications

References 10 publications

Altered β‐adrenergic response in mice lacking myotonic dystrophy protein kinase

Altered β‐adrenergic response in mice lacking myotonic dystrophy protein kinase

Two is better than one: A case of homozygous myotonic dystrophy type 1

Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus

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