Recessive Charcot-Marie-Tooth and multiple sclerosis associated with a variant in MCM3AP

Sedghi, Maryam; Moslemi, Ali‐Reza; Cabrera‐Serrano, Macarena; Ansari, Behnaz; Ghasemi, Majid; Baktashian, Mojtaba; Fattahpour, Ali; Tajsharghi, Homa

doi:10.1093/braincomms/fcz011

Cited by 4 publications

(2 citation statements)

References 37 publications

(45 reference statements)

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“…In addition, the Sac3 variant p.Ala867Asp has been found in combination with a nonsense variant p.Tyr899* in an Australian family (AUS cell line in this study) (2) ( Figure 1C). Furthermore, peripheral neuropathy and multiple sclerosis was associated with homozygous p.Ile954Thr variant (5). Amino acid conservation of the recessive Sac3 missense variants is shown in Supplementary material, Figure S3.…”

Section: Rnamentioning

confidence: 99%

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

Woldegebriel

Kvist

Andersson

et al. 2020

Human Molecular Genetics

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Defects in the mRNA export scaffold protein GANP, encoded by the MCM3AP gene, cause autosomal recessive early-onset peripheral neuropathy with or without intellectual disability. We extend here the phenotypic range associated with MCM3AP variants, by describing a severely hypotonic child and a sibling pair with a progressive encephalopathic syndrome. In addition, our analysis of skin fibroblasts from affected individuals from seven unrelated families indicates that disease variants result in depletion of GANP except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants. Patient fibroblasts showed transcriptome alterations that suggested intron content-dependent regulation of gene expression. For example, all differentially expressed intronless genes were downregulated, including ATXN7L3B, which couples mRNA export to transcription activation by association with the TREX-2 and SAGA complexes. Our results provide insight into the molecular basis behind genotype-phenotype correlations in MCM3AP-associated disease and suggest mechanisms by which GANP defects might alter RNA metabolism.

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Section: Rnamentioning

confidence: 99%

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

Woldegebriel

Kvist

Andersson

et al. 2020

Human Molecular Genetics

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show abstract

“…9,10 It also has been found in individuals with immunodeficiency, 12 intellectual disability, 13 Alzheimer disease, 14 vascular pathologies, [15][16][17] multiple sclerosis, 17 and Charcot-Marie-Tooth disease. 4,[18][19][20] There is preliminary evidence to suggest pleiotropy in the MCM3AP gene responsible for a periodic paralysis phenotype. In 2019, Gustavasson et al reported a pathogenic MCM3AP variant segregating in a Norwegian family diagnosed with periodic paralysis.…”

Section: Clinical Neuromuscular Diseasementioning

confidence: 99%

Two Cases of Periodic Paralysis Associated With MCM3AP Variants

Oishi,

Pagano,

Sellers

et al. 2023

Journal of Clinical Neuromuscular Disease

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Objectives: Periodic paralysis is a rare genetic condition characterized by episodes of neuromuscular weakness, often provoked by electrolyte abnormalities, physiologic stress, physical exertion, and diet. In addition to mutations in genes coding for skeletal muscle ion channels, in 2019, Gustavasson et al discovered that the MCM3AP gene could be responsible for periodic paralysis. In this study, we present 2 individuals with clinical episodes of periodic paralysis who have variants in the MCM3AP gene. Methods: Two unrelated probands were independently evaluated with clinical, genetic, and electrodiagnostic testing. Results: Proband 1 is a 46-year-old man who presented with decades of ongoing episodic weakness and fatigue, clinically diagnosed with periodic paralysis and supported by electrodiagnostic studies. Proband 2 is a 34-year-old woman with a history of episodic paralysis since childhood. Genetic testing in both individuals revealed potentially pathogenic variants in the MCM3AP gene. Conclusions: Periodic paralysis is a condition that significantly affects the lives of those diagnosed. The results illustrate that MCM3AP gene variants can been associated with a clinical and electrodiagnostic presentation of periodic paralysis. Additional future research should focus on clarifying any relationship between these genetic variants and the disease, as well as other possible genetic causes.

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Mutational analysis of minichromosome maintenance complex component ( MCM ) family genes in Chinese Han women with polycystic ovarian syndrome

Zhou

Liu

Tian

et al. 2023

Gynecological Endocrinology

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Recessive Charcot-Marie-Tooth and multiple sclerosis associated with a variant in MCM3AP

Cited by 4 publications

References 37 publications

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

Two Cases of Periodic Paralysis Associated With MCM3AP Variants

Mutational analysis of minichromosome maintenance complex component ( MCM ) family genes in Chinese Han women with polycystic ovarian syndrome

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