Marked Hemiatrophy in Carriers of Duchenne Muscular Dystrophy

Rajakulendran, Sanjeev; Küntzer, Thierry; Dunand, Murielle; Yau, Shu; Ashton, Emma; Storey, Helen; McCauley, Joanna; Abbs, Stephen; Thonney, F.; Lobrinus, Johannes Alexander; Yousry, Tarek; Farmer, Simon F.; Holton, Janice L.; Hanna, Michael G.

doi:10.1001/archneurol.2010.58

Cited by 10 publications

(12 citation statements)

References 7 publications

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“…This early event could explain the preferential segregation of dystrophin‐negative fibers on that side. However, we cannot exclude a contribution of somatic mosaicism in some of our cases, as already suggested in patients with marked hemiatrophy .…”

Section: Discussionmentioning

confidence: 52%

Muscle MRI in female carriers of dystrophinopathy

Tasca

Monforte

Iannaccone

et al. 2012

Euro J of Neurology

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The pattern we describe here is similar to that reported in Duchenne and Becker muscular dystrophy, although asymmetry represents a major distinctive feature. Muscle MRI was more sensitive than clinical examination for detecting single muscle involvement and asymmetry. Further studies are needed to verify the consistency of this pattern in larger cohorts and to assess whether muscle MRI can improve diagnostic accuracy in carriers with normal dystrophin staining on muscle biopsy.

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Section: Discussionmentioning

confidence: 52%

Muscle MRI in female carriers of dystrophinopathy

Tasca

Monforte

Iannaccone

et al. 2012

Euro J of Neurology

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“…This pattern is typically seen with female carriers of DMD, 8 however, the proband was male. Histopathology showed a remarkably variable dystrophic myopathy, with some regions showing normal histology, and others a marked dystrophic picture by both hematoxylin eosin and Gomori's-modified trichome methods (Figure 1c).…”

Section: Case Reportmentioning

confidence: 74%

Somatic mosaicism due to a reversion variant causing hemi-atrophy: a novel variant of dystrophinopathy

Punetha¹,

Mansoor²,

Bertorini³

et al. 2016

Eur J Hum Genet

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We describe a case of hemi-atrophy in a young adult male, with a positive family history of three maternal uncles with Duchenne muscular dystrophy (DMD). The patient showed progressive weakness localized to the left side, an abnormal electromyography, and creatine kinase levels 43000 IU/l. Muscle biopsy showed both dystrophin-positive and -negative myofibers. An out-of-frame duplication variant in DMD, that is, c.(93+1_94-1)_(649+1_650-1)dup(p.?) resulting in duplication of exons 3-7 was inherited, but the muscle biopsy showed dystrophin mRNA with and without the duplication. Dystrophin quantification using mass spectrometry showed 25% normal dystrophin protein levels in the muscle biopsy from the stronger right side. Sex chromosome aneuploidy was ruled out. We conclude that the patient inherited the duplication variant, but early in development an inner cell mass underwent a somatic recombination event removing the duplication and restoring dystrophin expression. To our knowledge, this is the first report of a reversion leading to somatic mosaicism in DMD.

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“…More recently, Rajakulendran et al [] reported on two unrelated women exhibiting hemiatrophy due to Duchenne muscular dystrophy (DMD), showing striking muscle wasting of right arm and leg. The authors reported co‐existence of reduced dystrophin and increased utrophin expression in scattered fibers from the right quadriceps biopsies in Patient 1, and a mosaic expression of dystrophin‐positive and dystrophin‐negative fibers in the right‐sided affected deltoid muscle biopsies in Patient 2 whose left‐sided muscles only showed “sporadic” dystrophin‐negative fibers.…”

Section: Resultsmentioning

confidence: 99%

“…A literature search was conducted for all molecular genetics, cytogenetics, and cell biology studies on mutation‐induced morphological, physiological, and developmental asymmetries. This survey yielded papers reporting the distributions of male and female cells in bilateral gynandromorphic animals [Agate et al, ; Zhao et al, ], and in human hermaphrodites [Gartler et al, ], the distributions of labeled cells in cell lineage traced animals [Klein, ; Danilchik and Black, ; Masho, ; Summers et al, ; Nutt et al, ], the distributions of the mutation‐carrying cells in patients with mutation‐induced diseases that affected an entire or almost one entire lateral body half of the patients [König et al, ; Li et al, ; Rajakulendran et al, ], and mutation‐carrying cell allocations in MZ twins of complete discordance [Sakuntabhai et al, ; Kondo et al, ; Robertson et al, ; Vadlamudi et al, ], partial discordance [Costa et al, ; Weksberg et al, ; Bliek et al, ], and mirror‐image discordance [Morison et al, ; Helland and Wester, ; Zhou et al, ]. Images depicting the distributions of morphological asymmetries and labeled cells were visually inspected and interpreted.…”

Section: Methodsmentioning

confidence: 99%

“…He posited that traits become manifest only when an early postzygotic mutation occurs, causing loss of the corresponding wild‐type (WT) allele [Happle, ]. Although somatic mutations that have been found to cause diseases exhibit mosaic phenotypes in some patients [Weinstein et al, ; Schwindinger et al, ; Poblete‐Gutierrez et al, ], the prevailing theories cannot explain why mutations and their corresponding phenotypes are confined to almost one entire lateral half of the body in some patients [Happle et al, ; König et al, ; Li et al, ; Rajakulendran et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Embryonic left–right separation mechanism allows confinement of mutation‐induced phenotypes to one lateral body half of bilaterians

Ma¹

2013

American J of Med Genetics Pt A

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A fundamental question in developmental biology is how a chimeric animal such as a bilateral gynandromorphic animal can have different phenotypes confined to different lateral body halves, and how mutation-induced phenotypes, such as genetic diseases, can be confined to one lateral body half in patients. Here, I propose that embryos of many, if not all, bilaterian animals are divided into left and right halves at a very early stage (which may vary among different types of animals), after which the descendants of the left-sided and right-sided cells will almost exclusively remain on their original sides, respectively, throughout the remaining development. This embryonic left-right separation mechanism allows (1) mutations and the mutation-induced phenotypes to be strictly confined to one lateral body half in animals and humans; (2) mothers with bilateral hereditary primary breast cancer to transmit their disease to their offspring at twofold of the rate compared to mothers with unilateral hereditary breast cancer; and (3) a mosaic embryo carrying genetic or epigenetic mutations to develop into either an individual with the mutation-induced phenotype confined unilaterally, or a pair of twins displaying complete, partial, or mirror-image discordance for the phenotype. Further, this left-right separation mechanism predicts that the two lateral halves of a patient carrying a unilateral genetic disease can each serve as a case and an internal control, respectively, for genetic and epigenetic comparative studies to identify the disease causations.

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Marked Hemiatrophy in Carriers of Duchenne Muscular Dystrophy

Cited by 10 publications

References 7 publications

Muscle MRI in female carriers of dystrophinopathy

Muscle MRI in female carriers of dystrophinopathy

Somatic mosaicism due to a reversion variant causing hemi-atrophy: a novel variant of dystrophinopathy

Embryonic left–right separation mechanism allows confinement of mutation‐induced phenotypes to one lateral body half of bilaterians

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