Correlation between
            <i>PABPN1</i>
            genotype and disease severity in oculopharyngeal muscular dystrophy

Richard, P.; Trollet, Capucine; Stojkovic, Tanya; Becdelièvre, Alix de; Périé, Sophie; Pouget, Jean; Eymard, B.; Filnemus,

doi:10.1212/wnl.0000000000003554

Cited by 53 publications

(59 citation statements)

References 25 publications

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“…These five groups were defined based on previous publications in which clinical features of OPMD were analysed 2. Our objective in developing this score was solely to classify clinical status in order to correlate patients’ symptoms with whole body MRI results.…”

Section: Methodsmentioning

confidence: 99%

Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

Alonso‐Jiménez

Kroon

Alejaldre-Monforte

et al. 2018

J Neurol Neurosurg Psychiatry

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Background and objectiveOculopharyngeal muscular dystrophy (OPMD) is a genetic disorder caused by an abnormal expansion of GCN triplets within the PABPN1 gene. Previous descriptions have focused on lower limb muscles in small cohorts of patients with OPMD, but larger imaging studies have not been performed. Previous imaging studies have been too small to be able to correlate imaging findings to genetic and clinical data.MethodsWe present cross-sectional, T1-weighted muscle MRI and CT-scan data from 168 patients with genetically confirmed OPMD. We have analysed the pattern of muscle involvement in the disease using hierarchical analysis and presented it as heatmaps. Results of the scans were correlated with genetic and clinical data.ResultsFatty replacement was identified in 96.7% of all symptomatic patients. The tongue, the adductor magnus and the soleus were the most commonly affected muscles. Muscle pathology on MRI correlated positively with disease duration and functional impairment.ConclusionsWe have described a pattern that can be considered characteristic of OPMD. An early combination of fat replacement in the tongue, adductor magnus and soleus can be helpful for differential diagnosis. The findings suggest the natural history of the disease from a radiological point of view. The information generated by this study is of high diagnostic value and important for clinical trial development.

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Section: Methodsmentioning

confidence: 99%

Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

Alonso‐Jiménez

Kroon

Alejaldre-Monforte

et al. 2018

J Neurol Neurosurg Psychiatry

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“…Remarkably, a small percentage of OPMD presents in an autosomal recessive manner wherein affected individuals are homozygous for alleles of 7 repeats. Evidence does not support anticipation in OPMD, but there is some support for a correlation between repeat length and disease severity (113). …”

Section: Introductionmentioning

confidence: 99%

Repeat expansion diseases

Paulson

2018

Neurogenetics, Part I

303

286

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More than 40 diseases, most of which primarily affect the nervous system, are caused by expansions of simple sequence repeats dispersed throughout the human genome. Expanded trinucleotide repeat diseases were discovered first and remain the most frequent. More recently tetra-, penta-, hexa-, and even dodeca-nucleotide repeat expansions have been identified as the cause of human disease, including some of the most common genetic disorders seen by neurologists. Repeat expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the most common genetic cause of amyotrophic lateral sclerosis/frontotemporal dementia (C9ORF72), Huntington disease, and eight other polyglutamine disorders, including the most common forms of dominantly inherited ataxia, the most common recessive ataxia (Friedreich ataxia), and the most common heritable mental retardation (fragile X syndrome). Here I review distinctive features of this group of diseases that stem from the unusual, dynamic nature of the underlying mutations. These features include marked clinical heterogeneity and the phenomenon of clinical anticipation. I then discuss the diverse molecular mechanisms driving disease pathogenesis, which vary depending on the repeat sequence, size, and location within the disease gene, and whether the repeat is translated into protein. I conclude with a brief clinical and genetic description of individual repeat expansion diseases that are most relevant to neurologists.

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“…Further study is needed to determine whether VCP mutations are found in other OPDM patients . In addition, the differential diagnosis of patients with myopathy affecting pharyngeal and ocular muscles should include progressive external ophthalmoplegia associated mitochondrial syndromes, oculopharyngeal muscular dystrophy, and myotonic dystrophy …”

Section: Discussionmentioning

confidence: 99%

VCP myopathy: A family with unusual clinical manifestations

et al. 2019

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Introduction: Valosin-containing protein (VCP) variants that affect muscle, bone, and the nervous system are termed multisystem proteinopathy. VCP myopathy is manifested as limb-girdle weakness, distal weakness and scapuloperoneal weakness. Methods: We reviewed clinical, genetic, and muscle biopsy data from 6 members of a family with VCP myopathy. Results: Clinical features of family members were complex and included dementia, myopathy, and hearing impairment. Ophthalmoplegia, ptosis, and dysphagia were present in 3 siblings. Rimmed vacuoles were observed in muscle biopsies, consistent with the pathological changes of VCP myopathy. A heterozygous VCP c.463C>A (p.R155S) that segregated in an autosomaldominant pattern was identified by genetic analysis. Conclusions: VCP myopathy can cause unusual manifestations that include ophthalmoplegia, ptosis, and dysphagia. This study increased our understanding of the clinical manifestations of VCP myopathy.Muscle Nerve 59: [365][366][367][368][369] 2019 Additional supporting information may be found in the online version of this article.

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Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy

Cited by 53 publications

References 25 publications

Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

Repeat expansion diseases

VCP myopathy: A family with unusual clinical manifestations

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