Uniparental disomy as a cause of spinal muscular atrophy and progressive myoclonic epilepsy: Phenotypic homogeneity due to the homozygous c.125C&gt;T mutation in ASAH1

Giráldez, Beatriz G.; Guerrero, Rosa; Ortega-Moreno, Laura; Verdú, Alfonso; Carrascosa-Romero, M.C.; García-Campos, Óscar; García-Muñozguren, Susana; Pardal-Fernández, José Manuel; Serratosa, Joan

doi:10.1016/j.nmd.2014.11.007

Cited by 14 publications

(17 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis of this model revealed a marked defect in motor neuron axonal branching associated with a significant increase in apoptosis in the spinal cord (Zhou et al, 2012). For other SMA-PME patients reported to date, ASAH1 mutations were identified using sanger or wholeexome sequencing (Rubboli et al, 2015;Dyment et al, 2014Dyment et al, , 2015Giráldez et al, 2015). The same c.125C>T mutation was identified in three additional patients, and other mutations including missense, non-sense, or large deletion of ASAH1 were identified (table 1).…”

Section: Sma-pme Is Caused By Mutations In Asah1mentioning

confidence: 95%

“…For other SMA‐PME patients reported to date, ASAH1 mutations were identified using sanger or whole‐exome sequencing (Rubboli et al ., ; Dyment et al ., , ; Giráldez et al ., ). The same c.125C>T mutation was identified in three additional patients, and other mutations including missense, non‐sense, or large deletion of ASAH1 were identified ( table ).…”

Section: Sma‐pme Is Caused By Mutations In Asah1mentioning

confidence: 97%

“…Based on the clinical description of cases reported to date (n = 11), SMA-PME is mainly characterized by progressive lower motor neuron degeneration followed by progressive myoclonic epilepsy (table 1) (Jankovic & Rivera, 1979;Haliloglu et al, 2002;Zhou et al, 2012;Dyment et al, 2014Dyment et al, , 2015Rubboli et al, 2015;Giráldez et al, 2015).…”

Section: Clinical Description Of Sma-pmementioning

confidence: 99%

“…SMA-PME is caused by mutation in the ASAH1 gene, which encodes acid ceramidase (Zhou et al, 2012). A total of 11 affected individuals have been reported thus far, leading to a relatively precise phenotypic characterization (Zhou et al, 2012;Dyment et al, 2014Dyment et al, , 2015Rubboli et al, 2015;Giráldez et al, 2015).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Spinal muscular atrophy associated with progressive myoclonus epilepsy

Topaloğlu

Melki

2016

Epileptic Disorders

View full text Add to dashboard Cite

A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as “spinal muscular atrophy associated with progressive myoclonic epilepsy” (SMA‐PME), has been described in childhood and is inherited as an autosomal recessive trait. SMA‐PME is caused by mutation in the ASAH1 gene encoding acid ceramidase. Ceramide and the metabolites participate in various cellular events as lipid mediators. The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. Three different ceramidases (acid, neutral and alkaline) have been identified and appear to play distinct roles in sphingolipid metabolism. The enzymatic activity of acid ceramidase is deficient in two rare inherited disorders; Farber disease and SMA‐PME. Farber disease is a very rare and severe autosomal recessive condition with a distinct clinical phenotype. The marked difference in disease manifestations may explain why Farber and SMA‐PME diseases were not previously suspected to be allelic conditions. The precise molecular mechanism underlying the phenotypic differences remains to be clarified. Recently, a condition with mutation in CERS1, the gene encoding ceramide synthase 1, has been identified as a novel form of PME. This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME.

show abstract

Section: Sma-pme Is Caused By Mutations In Asah1mentioning

confidence: 95%

Section: Sma‐pme Is Caused By Mutations In Asah1mentioning

confidence: 97%

Section: Clinical Description Of Sma-pmementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Spinal muscular atrophy associated with progressive myoclonus epilepsy

Topaloğlu

Melki

2016

Epileptic Disorders

View full text Add to dashboard Cite

show abstract

“…Autism spectrum disorder is a lifelong neurodevelopmental disorder characterized by deficits in social communication and interaction, repetitive and restrictive behavior, extensive clinical and etiologic heterogeneity, as well as, a remarkably rising global prevalence rate. A number of studies have provided evidence supporting the particular role of UPD in ASD, epilepsy and intellectual disability (ID) [4]. Furthermore, these neurodevelopmental conditions are also commonly associated with de novo This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.…”

Section: Introductionmentioning

confidence: 99%

Mosaic partial pericentromeric trisomy 8 and maternal uniparental disomy in a male patient with autism spectrum disorder

Ahram

Stambouli

Syrogianni

et al. 2016

Clinical Case Reports

View full text Add to dashboard Cite

Key Clinical MessageVarious chromosomal anomalies including small supernumerary marker chromosome (sSMC) and Uniparental disomy (UPD) have been described in association with intellectual disability and autism spectrum disorder. Based on our reported findings, we recommend that patients with sSMC(8) be evaluated for autism spectrum disorder (ASD) for early institution of therapy. In the presence of an identifiable sSMC, exploration of UPD is also recommended to further investigate the role of chromosome 8 UPD in ASD.

show abstract

The clinical spectrum of SMA‐PME and in vitro normalization of its cellular ceramide profile

Lee

McDowell

Vivo

et al. 2022

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA‐PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement. Methods Clinical features of 6 patients with SMA‐PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence‐based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase (rhAC) in vitro. Results The six new patients showed the hallmark features of SMA‐PME, with variable initial symptom and age of onset. Five of six patients carried at least one of the recurrent SMA‐PME variants observed in two specific codons of ASAH1. A review of 30 total cases revealed that patients who were homozygous for the most common c.125C > T variant presented in the first decade of life with limb‐girdle weakness as the initial symptom. Sensorineural hearing loss was associated with the c.456A > C variant. Leukocyte acid ceramidase activity varied from 4.1%–13.1% of controls. Ceramide species in fibroblasts were detected and total cellular ceramide content was elevated by 2 to 9‐fold compared to controls. Treatment with rhAC normalized ceramide profiles in cultured fibroblasts to control levels within 48 h. Interpretation This study details the genotype–phenotype correlations observed in SMA‐PME and shows the impact of rhAC to correct the abnormal cellular ceramide profile in cells.

show abstract

Uniparental disomy as a cause of spinal muscular atrophy and progressive myoclonic epilepsy: Phenotypic homogeneity due to the homozygous c.125C>T mutation in ASAH1

Cited by 14 publications

References 7 publications

Spinal muscular atrophy associated with progressive myoclonus epilepsy

Spinal muscular atrophy associated with progressive myoclonus epilepsy

Mosaic partial pericentromeric trisomy 8 and maternal uniparental disomy in a male patient with autism spectrum disorder

The clinical spectrum of SMA‐PME and in vitro normalization of its cellular ceramide profile

Contact Info

Product

Resources

About