BACKGROUND: Duchenne muscular dystrophy (DMD) patients are monitored periodically for cardiac involvement, including cardiac MRI with gadolinium-based contrast agents (GBCA). Texture analysis (TA) offers an alternative approach to assess late gadolinium enhancement (LGE) without relying on GBCA administration, impacting DMD patients' care. The study aimed to evaluate the prognostic value of selected TA features in the LGE assessment of DMD patients. RESULTS: We developed a pipeline to extract TA features of native T1 parametric mapping and evaluated their prognostic value in assessing LGE in DMD patients. For this evaluation, five independent TA features were selected using Boruta to identify relevant features based on their importance, least absolute shrinkage and selection operator (LASSO) to reduce the number of features, and hierarchical clustering to target multicollinearity and identify independent features. Afterward, logistic regression was used to determine the features with better discrimination ability. The independent feature inverse difference moment normalized (IDMN), which measures the pixel values homogeneity in the myocardium, achieved the highest accuracy in classifying LGE (0.857 (0.572-0.982)) and also was significantly associated with changes in the likelihood of LGE in a subgroup of patients with three yearly examinations (estimate: 23.35 (8.7), p-value = 0.008). Data are presented as mean (SD) or median (IQR) for normally and non-normally distributed continuous variables and numbers (percentages) for categorical ones. Variables were compared with the Welch t-test, Wilcoxon rank-sum, and Chi-square tests. A P-value < 0.05 was considered statistically significant. CONCLUSION: IDMN leverages the information native T1 parametric mapping provides, as it can detect changes in the pixel values of LGE images of DMD patients that may reflect myocardial alterations, serving as a supporting tool to reduce GBCA use in their cardiac MRI examinations.

• Keywords
• Cardiac MRI, Duchenne muscular dystrophy, Radiomics, Texture analysis,
• MeSH
• Child MeSH
• Muscular Dystrophy, Duchenne * diagnostic imaging   MeSH
• Gadolinium MeSH
• Contrast Media MeSH
• Humans MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Adolescent MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Gadolinium MeSH
• Contrast Media MeSH

BACKGROUND: ALG3-CDG is a rare autosomal recessive disease. It is characterized by deficiency of alpha-1,3-mannosyltransferase caused by pathogenic variants in the ALG3 gene. Patients manifest with severe neurologic, cardiac, musculoskeletal and ophthalmic phenotype in combination with dysmorphic features, and almost half of them die before or during the neonatal period. CASE PRESENTATION: A 23 months-old girl presented with severe developmental delay, epilepsy, cortical atrophy, cerebellar vermis hypoplasia and ocular impairment. Facial dysmorphism, clubfeet and multiple joint contractures were observed already at birth. Transferrin isoelectric focusing revealed a type 1 pattern. Funduscopy showed hypopigmentation and optic disc pallor. Profound retinal ganglion cell loss and inner retinal layer thinning was documented on spectral-domain optical coherence tomography imaging. The presence of optic nerve hypoplasia was also supported by magnetic resonance imaging. A gene panel based next-generation sequencing and subsequent Sanger sequencing identified compound heterozygosity for two novel variants c.116del p.(Pro39Argfs*40) and c.1060 C > T p.(Arg354Cys) in ALG3. CONCLUSIONS: Our study expands the spectrum of pathogenic variants identified in ALG3. Thirty-three variants in 43 subjects with ALG3-CDG have been reported. Literature review shows that visual impairment in ALG3-CDG is most commonly linked to optic nerve hypoplasia.

• Keywords
• ALG3-CDG, Arthrogryposis, Congenital disorder of glycosylation, N-linked glycosylation, Novel mutation, Optic nerve hypoplasia, Transferrin isoelectric focusing,
• MeSH
• Retinal Degeneration * MeSH
• Phenotype MeSH
• Infant MeSH
• Humans MeSH
• Mannosyltransferases genetics   MeSH
• Infant, Newborn MeSH
• Eye MeSH
• Child, Preschool MeSH
• Congenital Disorders of Glycosylation * genetics   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Review MeSH
• Names of Substances
• ALG3 protein, human MeSH Browser
• Mannosyltransferases MeSH

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by the lack of functional dystrophin. DMD is associated with progressive dilated cardiomyopathy, eventually leading to heart failure as the main cause of death in DMD patients. Although several molecular mechanisms leading to the DMD cardiomyocyte (DMD-CM) death were described, mostly in mouse model, no suitable human CM model was until recently available together with proper clarification of the DMD-CM phenotype and delay in cardiac symptoms manifestation. We obtained several independent dystrophin-deficient human pluripotent stem cell (hPSC) lines from DMD patients and CRISPR/Cas9-generated DMD gene mutation. We differentiated DMD-hPSC into cardiac cells (CC) creating a human DMD-CC disease model. We observed that mutation-carrying cells were less prone to differentiate into CCs. DMD-CCs demonstrated an enhanced cell death rate in time. Furthermore, ion channel expression was altered in terms of potassium (Kir2.1 overexpression) and calcium handling (dihydropyridine receptor overexpression). DMD-CCs exhibited increased time of calcium transient rising compared to aged-matched control, suggesting mishandling of calcium release. We observed mechanical impairment (hypocontractility), bradycardia, increased heart rate variability, and blunted β-adrenergic response connected with remodeling of β-adrenergic receptors expression in DMD-CCs. Overall, these results indicated that our DMD-CC models are functionally affected by dystrophin-deficiency associated and recapitulate functional defects and cardiac wasting observed in the disease. It offers an accurate tool to study human cardiomyopathy progression and test therapies in vitro.

• Keywords
• DMD, adrenergic response, cardiomyocyte death, cardiomyocytes, duchenne muscular dystrophy, excitation-contraction coupling, human pluripotent stem cells, intracellular calcium,
• Publication type
• Journal Article MeSH

BACKGROUND: The progressive cardiomyopathy that develops in boys with Duchenne and Becker muscular dystrophy (DMD/BMD) is presumed to be a secondary consequence of the fibrosis within the myocardium. There are only limited data on using parametric imaging in these patients. The purpose of this study was to assess native T1 and extracellular volume (ECV) values in DMD patients. METHODS: The Czech population of males with DMD/BMD was screened. All eligible patients fulfilling the inclusion criteria were included. Forty nine males underwent cardiac magnetic resonance (MR) examination including T1 native and post-contrast mapping measurements. One DMD patient and all BMD patients were excluded from statistical analysis. Three groups were compared - Group D1 - DMD patients without late gadolinium enhancement (LGE) (n = 23), Group D2 - DMD patients with LGE (n = 20), and Group C - gender matched controls (n = 13). RESULTS: Compared to controls, both DMD groups had prolonged T1 native relaxation time. These results are concordant in all 6 segments as well as in global values (1041 ± 31 ms and 1043 ± 37 ms vs. 983 ± 15 ms, both p < 0.05). Group D2 had significantly increased global ECV (0.28 ± 0.044 vs. 0.243 ± 0.013, p < 0.05) and segmental ECV in inferolateral and anterolateral segments in comparison with controls. The results were also significant after adjustment for subjects' age. CONCLUSION: DMD males had increased native T1 relaxation time independent of the presence or absence of myocardial fibrosis. Cardiac MR may provide clinically useful information even without contrast media administration.

• Keywords
• Cardiac magnetic resonance, Cardiomyopathy, Duchene muscular dystrophy, T1 mapping; extracellular volume,
• MeSH
• Muscular Dystrophy, Duchenne diagnostic imaging   MeSH
• Gadolinium analysis   MeSH
• Cardiomyopathies diagnostic imaging   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Adolescent MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Gadolinium MeSH