Nemaline Myopathy: Report of a Fatal Case, With Histochemical and Electron Microscopic Studies

Shafiq, Saiyid A.; Dubowitz, Victor; Peterson, Hart de C.; Milhorat, A. T.

doi:10.1093/brain/90.4.817

Cited by 104 publications

(20 citation statements)

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“…Notably, similar rod-like structures representing elongated dense bodies were frequently seen in visceral smooth muscle of Lmod1-null mice. Although they did not have the cross-striations of 145-Å periodicity seen in sarcomeric nemaline bodies, very similar structures were described in gastric smooth muscle of a patient diagnosed with nemaline myopathy (31). Of note, no such structures have yet been reported in patients with MMIHS.…”

Section: Discussionmentioning

confidence: 65%

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Halim

Wilson

Oliver

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

107

108

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Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal–contractile coupling.

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Section: Discussionmentioning

confidence: 65%

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Halim

Wilson

Oliver

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

107

108

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“…The ultrastructural finding of typical rods in our patient's muscle fibers indicate the neonatal form of nemaline myopathy. Eleven patients with neonatal nemaline myopathy who died during the first year of life have previously been presented, [1][2][3][4][5][6][7] but only two of theM6,7 have been identical in clinical features to our patient. Patients reported by McComb et al4 and Tsujihata et aF showed prematurity and dysmorphic features, but dysmorphic features were not described in the eight other reported infants with the neonatal form of nemaline myopathy.…”

Section: Discussionmentioning

confidence: 67%

Neonatal Form of Nemaline Myopathy, Muscle Immaturity, and a Microvascular Injury

1990

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An infant with a neonatal form of nemaline myopathy showed ultrastructural features of muscle immaturity. Immaturity was characterized by an abnormal presence of myotubes, as well as cells in clusters within a common basement membrane and a great number of satellite cells adhering to very small muscle fibers. In addition, degenerative changes and a severe microvascular lesion were observed. The pathologic findings in the muscle of this patient were those of neonatal nemaline myopathy complicating severe microvascular injury, possibly induced by an unknown toxic agent.

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“…The time of death was between a few hours and 11 months. In most of the cases there were no antenatal signs or only clinical signs (diminished fetal movements during the last trimester) [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Recent cases described ultrasonographic signs: reduced fetal movements and polyhydramnios [22][23][24][25]; severe polyhydramnios, absent fetal body and limb movements, inability to visualize the stomach and arthrogryposis of hands and feet [24]; clubfeet re-…”

Section: Discussionmentioning

confidence: 99%

Congenital Rapidly Fatal Form of Nemaline Myopathy with Fetal Hydrops and Arthrogryposis

Vardon

Chau²,

Sigodi³

et al. 1998

Fetal Diagn Ther

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A new lethal case of nemaline myopathy is reported. The diagnosis was made by postmortem muscle biopsy. The child died before his first day of life. This is one of the very rare cases of nemaline myopathy with severe antenatal ultrasonographic signs: fetal hydrops and arthrogryposis. In a review of the literature other cases of the congenital rapidly fatal form are found, some of them with clinical decrease of fetal movements but only few authors report ultrasonographic signs. The diagnostic, histopathogenic, genetic and evolutive aspects of this heterogeneous disorder are analyzed. This congenital nonprogressive myopathy is not as benign as previously thought and may be an etiology of the lethal form of arthrogryposis multiplex congenita. The existence of ultrasonographic antenatal signs seems to be a factor of poor prognosis. In spite of recent genetic discoveries, there is at present no specific antenatal diagnosis. Consequently, muscle biopsy in lethal cases is very important to allow a genetic counselling; however, in utero fetal biopsy has never been performed in such cases.

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Nemaline Myopathy: Report of a Fatal Case, With Histochemical and Electron Microscopic Studies

Cited by 104 publications

References 0 publications

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Neonatal Form of Nemaline Myopathy, Muscle Immaturity, and a Microvascular Injury

Congenital Rapidly Fatal Form of Nemaline Myopathy with Fetal Hydrops and Arthrogryposis

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