A recurrent homozygous missense <scp><i>DPM3</i></scp> variant leads to muscle and brain disease

Nagy, Sara; Lau, Tracy; Alavi, Shahryar; Karimiani, Ehsan Ghayoor; Vallian, Jalal; Ng, Bobby G.; Asl, Samaneh Noroozi; Akhondian, Javad; Bahreini, Amir; Yaghini, Omid; Uapinyoying, Prech; Bönnemann, Carsten G.; Freeze, Hudson H.; Dissanayake, Vajira H. W.; Sirisena, Nirmala D.; Schmidts, Miriam; Houlden, Henry; Moreno-De-Luca, Andrés; Maroofian, Reza

doi:10.1111/cge.14208

Cited by 4 publications

(2 citation statements)

References 13 publications

(42 reference statements)

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“…Limb-girdle muscular dystrophy-dystroglycanopathy type C15 (MDDGC15) [OMIM:612937] is an AR CDG caused by mutation on the dolichol-phosphate mannose synthase subunits 3 (DPM3) gene on chromosome 1q22. DPM3, together with DPM1 and DPM2, forms the DPM complex, which is responsible for the production of mannosyl donors for glycosylphosphatidylinositols, N-glycan synthesis, and protein O-/C-mannosylation [361]. Loss of function due to DPM3 gene mutations clinically results in a rare type of limb-girdle muscular dystrophy-dystroglycanopathy, presenting with progressive proximal muscle weakness and DCM.…”

Section: Dpm3-cdgmentioning

confidence: 99%

“…Loss of function due to DPM3 gene mutations clinically results in a rare type of limb-girdle muscular dystrophy-dystroglycanopathy, presenting with progressive proximal muscle weakness and DCM. Out of the 11 patients reported to date, four were described with DCM as the most predominant cardiac symptom and less frequently with mild LVD and LVRWMA [361][362][363] (Table 5, Supplementary Tables S2 and S3).…”

Section: Dpm3-cdgmentioning

confidence: 99%

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Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

Conte,

Sam,

Lefeber

et al. 2023

IJMS

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Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations. In this systematic review, we offer a comprehensive overview of IMDs linked to carbohydrate metabolism presenting that present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects. We identified 58 IMDs presenting with cardiac complications: 3 defects of sugar/sugar-linked transporters (GLUT3, GLUT10, THTR1); 2 disorders of the pentose phosphate pathway (G6PDH, TALDO); 9 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1); 29 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2); 15 carbohydrate-linked lysosomal storage diseases (CTSA, GBA1, GLA, GLB1, HEXB, IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, ARSB, GUSB, ARSK). With this systematic review we aim to raise awareness about the cardiac presentations in carbohydrate-linked IMDs and draw attention to carbohydrate-linked pathogenic mechanisms that may underlie cardiac complications.

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Section: Dpm3-cdgmentioning

confidence: 99%

Section: Dpm3-cdgmentioning

confidence: 99%

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

Conte,

Sam,

Lefeber

et al. 2023

IJMS

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A recurrent homozygous missense DPM3 variant leads to muscle and brain disease

et al. 2022

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Biallelic pathogenic variants in the genes encoding the dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein Oand C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual with compound heterozygous DPM3 variants presenting with myopathy, mild intellectual disability, seizures, and nonspecific white matter abnormalities (WMA) around the lateral ventricles has been described. Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures,

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Prognostic modeling of glycosylation in TNBC and screening of related key genes through a comprehensive analysis of multi-omics studies

Zhou,

Wang,

Guo

et al. 2023

Preprint

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Background The most common malignancy in women is breast cancer, and the prognosis varies greatly according to its typing, among which the worst prognosis is TNBC. The glycosylation is one of the most priorities among reasons influencing the prognosis with TNBC of patients. We aim to develop a tumor prognosis model by analyzing genes related to glycosylation in order to predict patient prognosis. Methods The dataset was downloaded from the TCGA databank and the predictive genes were identified through Cox one-way regression analysis. The model genes with the highest risk scores among the 18 samples were obtained by lasso regression analysis, and the model was established. The related pathways affecting the progression of TNBC were analyzed, and the key genes of the disease were discovered for subsequent research. Results The model was constructed using TCGA database data, and The model underwent verification through K-M curve analysis and ROC curve. Then, we analyzed that the high expression of tumor-related chemokines in high-risk group may be associated with poor tumor prognosis. Finally, We conducted a random survival forest analysis and identified two significant genes, namely DPM2 and PINK1, which have been selected for further investigation. Conclusion The prognostic analysis model constructed by the TNBC glycosylation gene has excellent validation efficacy. It can be used for prognostic analysis of relevant TNBC patients.

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A recurrent homozygous missense DPM3 variant leads to muscle and brain disease

Cited by 4 publications

References 13 publications

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease

Prognostic modeling of glycosylation in TNBC and screening of related key genes through a comprehensive analysis of multi-omics studies

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