A new congenital muscular dystrophy with mitochondrial structural abnormalities

Nishino, Ichizo; Kobayashi, Osamu; Goto, Yu‐ichi; Kurihara, Mana; Kumagai, Ken; Fujita, Takehisa; Hashimoto, Kiyoshi; Horai, Satoshi; Nonaka, Ikuya

doi:10.1002/(sici)1097-4598(199801)21:1<40::aid-mus6>3.0.co;2-g

Cited by 68 publications

(23 citation statements)

References 17 publications

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“…12 Only 2 out of the 12 genes, apart from SCO2 and TYMP, affected by the deletions are associated with human disease (Supplementary Table 1). Although mutations in both ARSA and CHKB result in autosomal recessive disorders, their clinical features, neonatal manifestation of cardiomyopathy with increased creatine kinase activity found in CHKB-related muscular dystrophy 15 or mental decline specific for juvenile form of metachromatic leukodystrophy, are distinct from symptoms observed in our patients.…”

Section: Discussioncontrasting

confidence: 55%

Large copy number variations in combination with point mutations in the TYMP and SCO2 genes found in two patients with mitochondrial disorders

et al. 2013

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Mitochondrial disorders are caused by defects in mitochondrial or nuclear DNA. Although the existence of large deletions in mitochondrial DNA (mtDNA) is well known, deletions affecting whole genes are not commonly described in patients with mitochondrial disorders. Based on the results of whole-genome analyses, copy number variations (CNVs) occur frequently in the human genome and may overlap with many genes associated with clinical phenotypes. We report the discovery of two large heterozygous CNVs on 22q13.33 in two patients with mitochondrial disorders. The first patient harboured a novel point mutation c.667G4A (p.D223N) in the SCO2 gene in combination with a paternally inherited 87-kb deletion. As hypertrophic cardiomyopathy (HCMP) was not documented in the patient, this observation prompted us to compare his clinical features with all 44 reported SCO2 patients in the literature. Surprisingly, the review shows that HCMP was present in only about 50% of the SCO2 patients with non-neonatal onset. In the second patient, who had mitochondrial neurogastrointestinal encephalopathy (MNGIE), a maternally inherited 175-kb deletion and the paternally inherited point mutation c.261G4T (p.E87D) in the TYMP gene were identified.

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Section: Discussioncontrasting

confidence: 55%

Large copy number variations in combination with point mutations in the TYMP and SCO2 genes found in two patients with mitochondrial disorders

et al. 2013

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“…Mutations in choline kinase B, which is involved in phosphatidylcholine biosynthesis, cause a congenital onset muscular dystrophy with large appearing mitochondria (megacolonial or giant mitochondria) on oxidative stains and ultrastructure [119]. Affected patients in addition show cognitive impairment but normal brain MRI findings and also skin findings including acanthosis nigricans like lesions with intense pruritus.…”

Section: Diagnostic Aspects Of Specific Subtypesmentioning

confidence: 99%

Diagnostic approach to the congenital muscular dystrophies

Bönnemann

Wang

Quijano‐Roy

et al. 2014

Neuromuscular Disorders

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Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis.

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“…83 The unusual muscle morphology, which included giant mitochondria that were displaced to the periphery of the fibres, was later observed in spontaneously mutant dystrophic mice that harboured changes in the gene encoding choline kinase-β ( Chkb ). 84 Sequencing of CHKB in 15 patients with the disorder revealed 11 pathogenic mutations.…”

Section: Disorders Of Ndna Defectsmentioning

confidence: 99%

The clinical maze of mitochondrial neurology

et al. 2013

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Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category—defects of mtDNA maintenance—combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot–Marie–Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed.

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A new congenital muscular dystrophy with mitochondrial structural abnormalities

Cited by 68 publications

References 17 publications

Large copy number variations in combination with point mutations in the TYMP and SCO2 genes found in two patients with mitochondrial disorders

Large copy number variations in combination with point mutations in the TYMP and SCO2 genes found in two patients with mitochondrial disorders

Diagnostic approach to the congenital muscular dystrophies

The clinical maze of mitochondrial neurology

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