Importance of Skin Changes in the Differential Diagnosis of Congenital Muscular Dystrophies

Yış, Uluç; Baydan, Figen; Karakaya, Mert; Kurul, Semra Hız; Çırak, Sebahattin

doi:10.1155/2016/3128735

Cited by 8 publications

(6 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cardiac involvement is relatively frequent (around 50%) in patients affected by megaconial CMD (15). One patient manifested epileptic seizures and the other two presented with ichthyosis-like skin changes similarly the two siblings studied by Yis in which was underlined the importance of this clinical aspect in the differential diagnosis of CMD (16). We observed a peculiar rearrangement of mitochondrial network and alterations of the mitochondrial inner ΔΨm in patients' derived cells.…”

Section: Discussionsupporting

confidence: 49%

Alteration of mitochondrial membrane inner potential in three Italian patients with megaconial congenital muscular dystrophy carrying new mutations in CHKB gene

et al. 2019

View full text Add to dashboard Cite

Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders presenting at birth with psychomotor delay, cognitive impairment, muscle weakness and hypotonia. Here we described an alteration of mitochondrial inner membrane potential and mitochondrial network in cells derived from Italian patients carrying three novel mutations in CHKB gene, recently associated with "megaconial CMD". On the bases of our findings, we hypothesize that the mitochondrial membrane potential alteration, presumably as a consequence of the altered biosynthesis of phosphatidylcholine, could be responsible for the peculiar morphological aspect of mitochondria in this disease and might be involved in the disease pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 49%

Alteration of mitochondrial membrane inner potential in three Italian patients with megaconial congenital muscular dystrophy carrying new mutations in CHKB gene

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Genomic DNA samples were extracted from peripheral blood following standard protocols. Whole exome sequencing was performed following exome enrichment using an Illumina HiSeq 2000 (Yis et al, 2016;Ahmed et al, 2017). Reads were analysed for exome coverage, SNP/InDel variant calling and quality assessment, resulting in 495% of targeted sequences covered for variant calling at 410Â coverage in each case.…”

Section: Genetic Studiesmentioning

confidence: 99%

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization

Wang

Salter

Refai

et al. 2017

Brain

Self Cite

View full text Add to dashboard Cite

The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection.

show abstract

“…Megaconial CMD is a distinct form of CMD with multisystem involvement and extraordinary mitochondrial structural changes, due to a disruption of a PC metabolism 2 , 3 . To the best of our knowledge, there are less than 50 patients reported worldwide, however there may be unreported cases 2 – 6 , 8 , 28 – 38 . The biggest cohort of patients are reported from Turkey, including the original gene identification report 1 , 2 .…”

Section: Discussionmentioning

confidence: 99%

Reduced mitochondrial fission and impaired energy metabolism in human primary skeletal muscle cells of Megaconial Congenital Muscular Dystrophy

Aksu-Menges

Eylem

Nemutlu

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Megaconial Congenital Muscular Dystrophy (CMD) is a rare autosomal recessive disorder characterized by enlarged mitochondria located mainly at the periphery of muscle fibers and caused by mutations in the Choline Kinase Beta (CHKB) gene. Although the pathogenesis of this disease is not well understood, there is accumulating evidence for the presence of mitochondrial dysfunction. In this study, we aimed to investigate whether imbalanced mitochondrial dynamics affects mitochondrial function and bioenergetic efficiency in skeletal muscle cells of Megaconial CMD. Immunofluorescence, confocal and transmission electron microscopy studies revealed impaired mitochondrial network, morphology, and localization in primary skeletal muscle cells of Megaconial CMD. The organelle disruption was specific only to skeletal muscle cells grown in culture. The expression levels of mitochondrial fission proteins (DRP1, MFF, FIS1) were found to be decreased significantly in both primary skeletal muscle cells and tissue sections of Megaconial CMD by Western blotting and/or immunofluorescence analysis. The metabolomic and fluxomic analysis, which were performed in Megaconial CMD for the first time, revealed decreased levels of phosphonucleotides, Krebs cycle intermediates, ATP, and altered energy metabolism pathways. Our results indicate that reduced mitochondrial fission and altered mitochondrial energy metabolism contribute to mitochondrial dysmorphology and dysfunction in the pathogenesis of Megaconial CMD.

show abstract

Importance of Skin Changes in the Differential Diagnosis of Congenital Muscular Dystrophies

Cited by 8 publications

References 9 publications

Alteration of mitochondrial membrane inner potential in three Italian patients with megaconial congenital muscular dystrophy carrying new mutations in CHKB gene

Alteration of mitochondrial membrane inner potential in three Italian patients with megaconial congenital muscular dystrophy carrying new mutations in CHKB gene

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization

Reduced mitochondrial fission and impaired energy metabolism in human primary skeletal muscle cells of Megaconial Congenital Muscular Dystrophy

Contact Info

Product

Resources

About