Novel mutations in <i>DPM3</i> cause dystroglycanopathy with central nervous system involvement

Jun, Fu; Ma, Mingming; Song, Jia; Pang, Ming; Yang, Liang-Tung; Li, Gang; Zhang, Jiewen

doi:10.1111/cge.13634

Cited by 4 publications

(6 citation statements)

References 5 publications

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“…2,11,12 Interestingly, the homozygous p.(Tyr74Cys) variant is located on a transmembrane domain next to p.(Pro72Ala) variant which was identified as compound het with p.(Leu115Ter) in the girl with muscle and brain presentation. 7 However, the biochemical assay could not detect any changes in the N-glycosylation pathway, which correlates with previous findings stating that the transmembrane domain is not necessary for the enzymatic activity of the complex. 12 In contrast, the highly conserved coiled-coil region was shown to be required for the enzymatic process, and variant in this domain was associated with reduced O-mannosylation of alpha-dystroglycan due to reduced binding capacity of DPM3 for DPM1.…”

Section: Discussionsupporting

confidence: 89%

“…Additionally, two patients presented with cardiomyopathy. The brain MRI of the patients showed periventricular WMA similar to the patient of Fu et al, 7 however, we also identified WMA in the subcortical region and WM volume loss. Thus, we conclude this new and pathogenic variant in DPM3 can lead to congenital muscle and brain disease.…”

Section: Discussionsupporting

confidence: 85%

“…Affected individuals with DPM1 and DPM2 variants frequently show central nervous system involvement, 1 thus, one would expect a similar phenotype in DPM3 . Nevertheless, only one individual has been reported with DPM3 ‐related dystroglycanopathy and WMA on brain MRI, 7 and Lefeber et al reported stroke‐like episodes in a patient with DPM3‐related muscle dystrophy 2 . Hereby we describe five patients with a genetically confirmed homozygous variant in DPM3 , presenting with muscle involvement along with WMA, DD/ID, and epilepsy.…”

Section: Discussionmentioning

confidence: 78%

“…Biallelic variants in DPM subunits 1 and 2 (DPM1, MIM 608799; DPM2, MIM 615042) are known to be associated with muscle-eyebrain (MEB) disease, 1 while biallelic variants in DPM3 (MIM 612937) were initially described only in the context of muscle dystrophy and cardiomyopathy. [2][3][4][5][6] In 2019, Fu et al 7…”

Section: Introductionmentioning

confidence: 99%

“…Biallelic variants in DPM subunits 1 and 2 ( DPM1 , MIM 608799 ; DPM2 , MIM 615042) are known to be associated with muscle–eye–brain (MEB) disease, 1 while biallelic variants in DPM3 (MIM 612937) were initially described only in the context of muscle dystrophy and cardiomyopathy 2–6 . In 2019, Fu et al 7 presented the first patient, a Chinese girl with combined muscle and central nervous system involvement due to compound heterozygous variants in DPM3 . Here we report three unrelated Iranian families and one from Sri Lanka with five children presenting with congenital muscle weakness, developmental delay (DD)/intellectual disability (ID), and epilepsy due to an ultra‐rare homozygous missense DPM3 variant.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Congenital Muscular Dystrophies

McMillan,

Oskoui

2023

Current Clinical Neurology

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Epidemiology of congenital disorders of glycosylation (CDG)—overview and perspectives

et al. 2022

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Background and aim Congenital disorders of glycosylation (CDG) are a large heterogeneous group of about 170 rare inherited metabolic disorders due to defective protein and lipid glycosylation. This study aimed to assemble and summarise available data on the epidemiology of CDG. Methods A set of keywords related to epidemiology and CDG was defined. The keywords were combined through a custom Python script, search through the MEDLINE database, using PubMed as the search engine. The script retrieved the correspondent MEDLINE data from each article, and the relevant information was exported. Next, inclusion and exclusion criteria were set and applied during the selection phase. Finally, epidemiology-related information was extracted and compiled. Results One hundred sixty-five papers on CDG epidemiology were included in this literature review. Most of them reported on the frequency of symptoms in CDG patients followed in cohort studies, on pathogenic variant allelic frequency, and on the prevalence of the disorder in populations. According to this review, the most reported CDG was phosphomannomutase-2 deficiency (PMM2-CDG) followed in descending order by FKTN-CDG, EXT1/EXT2-CDG, ALG6-CDG, and PIGA-CDG. Conclusions We provide an overview on epidemiological data regarding 93 CDG by compiling information from the literature. Generating epidemiological data on CDG is important to appropriately target resources for CDG research and drug development and to support public health decision-making.

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Novel mutations in DPM3 cause dystroglycanopathy with central nervous system involvement

Cited by 4 publications

References 5 publications

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

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

Congenital Muscular Dystrophies

Epidemiology of congenital disorders of glycosylation (CDG)—overview and perspectives

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