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Updated: May 14, 2026
Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy
Published on: January 12, 2019
Relationship Between Dp140 Genotype and Cortical Similarity Network Phenotype in Duchenne Muscular Dystrophy:
Suming Zhang1, Xiaoyu Niu1, Qing Hu2
1Department of Radiology, Key Laboratory of Obstetric & Gynecologic and Pediatric Disease and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Background:
Dp140-related mutations associate with neurodevelopmental impairments in Duchenne muscular dystrophy (DMD), their effects on cortical similarity network organization remain unclear.
Purpose:
To characterize alterations in morphometric similarity networks (MSN) in DMD with different Dp140 genotypes, assess their associations with clinical phenotypes and gene expression.
Study Type:
Prospective.
Population:
One hundred and fifteen boys with DMD (75 Dp140-: 9.63 ± 2.25 years; 40 Dp140+: 10.99 ± 2.25 years) and 69 healthy controls (all male, 10.65 ± 2.43 years).
Field Strength/Sequence:
Gradient echo at 3 T.
Assessment:
MRI were processed using FreeSurfer and GRETNA. Behavior data were based on Wechsler Intelligence Scale for children-Fourth edition while transcriptional profiles were from the Allen Human Brain Atlas.
Statistical Tests:
Independent T-tests, chi-square tests, general linear models, permutation testing, multivariable linear regression, mediation analyses, partial least squares regression, spatial permutation tests (Spin test), Gene Ontology enrichment analysis and cell-type analysis. FDR-corrected p < 0.05 and p spin < 0.05 were considered significant.
Results:
Dp140- subgroup had lower working memory index (WMI) than Dp140+ DMD (81.63 ± 15.48 vs. 90.78 ± 15.31; p = 0.01, Cohen's d = 0.179). Dp140- DMD showed reduced cortical similarity in bilateral lateral prefrontal cortex and parietal cortex regions, increased modular segregation (Hedge's g = -0.298, 95% CI [-0.408, -0.187]), and more hubs loss within frontal parietal network (FPN). The indirect effect of Dp140 genotype on WMI through mean FPN cortical similarity was significant (β = -0.121, p = 0.03, 95% CI [-0.282, -0.001]). The Dp140-specific MSN changes were spatially associated with transcriptional profile, which are enriched in neuronal projection development pathways of excitatory neurons (p spin < 0.05).
Data Conclusion:
By linking genotype, neuroimaging, and transcriptional data, these findings offer further insight into mechanisms possibly involved in working memory deficits among Dp140- DMD.
Evidence Level:
2.
Technical Efficacy:
Stage 2.
