Mental retardation in Duchenne muscular dystrophy

Nardes, Flávia; Araujo, Anna Carla; Ribeiro, Márcia Gonçalves

doi:10.2223/jped.2148

Cited by 31 publications

(23 citation statements)

References 42 publications

(25 reference statements)

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“…In the original description of the disease circa 1861, Duchenne reported 5 patients with some degree of cognitive defects [6]. Since then, an overwhelming amount of evidence has shown that there can be a significant cognitive impairment in DMD patients [7;8]; mental retardation affects around 30% of boys with DMD [9]. Impaired memory function, especially restricted verbal short term memory, seems to characterize the neuropsychological profile of many patients with DMD [10;11].…”

Section: Introductionmentioning

confidence: 99%

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Shi

Pratt

et al. 2015

Neuromuscular Disorders

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Duchenne muscular dystrophy (DMD), an X-linked disorder caused by the lack of dystrophin, is characterized by the progressive wasting of skeletal muscles. To date, what is known about dystrophin function is derived from studies of dystrophin-deficient animals, with the most common model being the mdx mouse. Most studies on patients with DMD and in mdx mice have focused on skeletal muscle and the development of therapies to reverse, or at least slow, the severe muscle wasting and progressive degeneration. However, dystrophin is also expressed in the CNS. Both mdx mice and patients with DMD can have cognitive and behavioral changes, but studies in the dystrophic brain are limited. We examined the brain structure and metabolites of mature wild type (WT) and mdx mice using magnetic resonance imaging and spectroscopy (MRI/MRS). Both structural and metabolic alterations were observed in the mdx brain. Enlarged lateral ventricles were detected in mdx mice when compared to WT. Diffusion tensor imaging revealed elevations in diffusion diffusivities in the prefrontal cortex and a reduction of fractional anisotropy in the hippocampus. Metabolic changes included elevations in phosphocholine and glutathione, and a reduction in γ-aminobutyric acid in the hippocampus. In addition, an elevation in taurine was observed in the prefrontal cortex. Such findings indicate a regional structural change, altered cellular antioxidant defenses, a dysfunction of GABAergic neurotransmission, and a perturbed osmoregulation in the brain lacking dystrophin.

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Section: Introductionmentioning

confidence: 99%

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Shi

Pratt

et al. 2015

Neuromuscular Disorders

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“…While for some forms of MD, the initial symptoms manifested begin with childhood and have a rapid progression of muscle weakness causing the death of the patients around the age of 20 years, the other forms debut later in adulthood [4,5] and have a slow rate of progression and an almost normal lifetime [6,7]. Also, heart disease and mental retardation accompany some types of MD [8,9], suggesting a different pathogenesis of the disease. It also found that there are subtypes of MD that share similar clinical manifestations and different genetic defects with similar clinical manifestation [10,11].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Molecular Diagnosis in Muscular Dystrophies

Găină¹,

Budişteanu²,

Manole³

et al. 2019

Muscular Dystrophies

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Muscular dystrophies are a diverse group of inherited muscle disorders with a wide range of clinical manifestations from a severe form with early onset and early death to adult forms with later onset and minimal clinical manifestation that do not affect lifespan. Overlapping clinical symptoms and the multitude of genes that need to be analyzed for an accurate characterization make the diagnosis hard. In next-generation sequencing era, a lot of used assay in molecular diagnostics must be taken into consideration for muscular dystrophy diagnosis. However,formoreaccuratediagnosis,muscle protein expressions analysis may have prognostic value. In this chapter, we present the most important clinical and laboratory findings in the most common forms of muscular dystrophies and molecular diagnostic approaches for a more accurate diagnosis.

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“…Approximately 1/3 of cases arise from spontaneous mutations (Nardes et al , 2012, Selsby et al , 2015). The correlation between mutation and phenotype is better explained by the reading frame theory of Monaco (Monaco et al , 1988).…”

Section: Introductionmentioning

confidence: 99%

Duchenne and Becker Muscular Dystrophies: A Review of Animal Models, Clinical End Points, and Biomarker Quantification

Wilson¹,

Faelan²,

Patterson-Kane³

et al. 2017

Toxicol Pathol

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Duchenne and Becker muscular dystrophies (DMD/BMD) are neuromuscular disorders that primarily affect boys due to an X-linked mutation in the DMD gene, resulting in reduced to near absence of dystrophin or expression of truncated forms of dystrophin. Some newer therapeutic interventions aim to increase sarcolemmal dystrophin expression, and accurate dystrophin quantification is critical for demonstrating pharmacodynamic relationships in preclinical studies and clinical trials. Current challenges with measuring dystrophin include the variation in protein expression within individual muscle fibers and across whole muscle samples, the presence of pre-existing dystrophin-positive revertant fibers, and trace amounts of residual dystrophin. Immunofluorescence quantification of dystrophin can overcome many of these challenges, but manual quantification of protein expression may be complicated by variations in the collection of images, reproducible scoring of fluorescent intensity, and bias introduced by manual scoring of typically only a few high-power fields. This review highlights the pathology of DMD/BMD, discusses animal models of DMD/BMD, and describes dystrophin biomarker quantitation in DMD/BMD, with several image analysis approaches, including a new automated method, that evaluates protein expression of individual muscle fibers.

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Mental retardation in Duchenne muscular dystrophy

Cited by 31 publications

References 42 publications

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Clinical and Molecular Diagnosis in Muscular Dystrophies

Duchenne and Becker Muscular Dystrophies: A Review of Animal Models, Clinical End Points, and Biomarker Quantification

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