Congenital muscular dystrophy

Gene: DPM1

Amber List (moderate evidence)

DPM1 (dolichyl-phosphate mannosyltransferase subunit 1, catalytic)
EnsemblGeneIds (GRCh38): ENSG00000000419
EnsemblGeneIds (GRCh37): ENSG00000000419
OMIM: 603503, Gene2Phenotype
DPM1 is in 14 panels

7 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

At least 12 individuals from 10 unrelated families described in literature. 8/12 individuals had variably elevated CK levels, as well as hypotonia. CK levels were normal in 4 cases. Only one individual showed muscular dystrophy on muscle biopsy (PMID: 23856421) and another had a myopathic electromyogram (PMID: 30653653). However, muscle biopsy was normal in 1 patient (PMID: 15669674).

Although high levels of CK can indicate damage or disease of the skeletal muscles, I'm not sure that this alone is sufficient evidence for inclusion of DPM1 as the testing criteria for this panel includes muscle biopsy or muscle/brain MRI results indicative of muscular dystrophy, which has only been confirmed in a single case to date.

Therefore, maintaining Amber rating pending further evidence (added watchlist tag)
Created: 2 Jul 2021, 10:30 a.m. | Last Modified: 2 Jul 2021, 10:30 a.m.
Panel Version: 2.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ie, OMIM:608799

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

PMID: 23856421 - neonatal onset of muscular dystrophy confirmed by muscle biopsy, elevated CK levels

PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and had elevated CK levels.

Four families with hypotonia and raised CK.
Created: 24 Jun 2020, 8:33 a.m. | Last Modified: 24 Jun 2020, 8:33 a.m.
Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Ie 608799

Publications

Variants in this GENE are reported as part of current diagnostic practice

Louise Daugherty (Genomics England Curator)

I don't know

Only one case reported with variants in this gene and CMD, not sure it fulfils the criteria to be a green gene. Provisional rated Amber pending further cases or expert opinion.
Created: 14 Oct 2019, 2:02 p.m. | Last Modified: 14 Oct 2019, 2:02 p.m.
Panel Version: 1.65
Initial gene list (Congenital Muscular Dystrophy Gene Panel 207-London South GLH.xlsx) collated by Rachael Mein, Viapath Guy's Hospital February 2019 on behalf of London South GLH for the GMS Neurology specialist test group.
Created: 29 Apr 2019, 3:37 p.m.

Rachael Mein (Viapath at Guy's Hospital)

Green List (high evidence)

PMID:23856421 - an infant with the phenotype of a congenital muscular dystrophy, with borderline microcephaly, hypotonia, camptodactyly, severe motor delay, and elevated creatine kinase. Muscle biopsy showed muscular dystrophy and reduced -dystroglycan immunostaining with glycoepitope-specific antibodies in a pattern diagnostic of dystroglycanopathy. The infant was compound heterozygous for a novel missense variant and an intragenic deletion from exons 3-7. In vitro studies showed decreased DPM1 activity in fibroblasts, and reduced binding to DPM3; PMID:23109149 - DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies
Created: 29 Apr 2019, 3:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
congenital muscular dystrophies; Congenital disorder of glycosylation, type Ie 608799

Publications

Variants in this GENE are reported as part of current diagnostic practice

Arianna Tucci (Genomics England Curator)

I don't know

Possible phenotypic overlap with CMD and good functional data. only one case reported with mutations in this gene and CMD. Hence, worth following up possible cause of CMD in a research setting, but I am not sure it fulfils the criteria to be a green gene
Created: 26 Jan 2017, 2:51 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Keep amber for now, as both reviewers are unsure whether there is enough evidence for this to be green.
Created: 27 Jan 2017, 1:45 p.m.
Comment on list classification: Promoted to amber - clear evidence for association with congenital disorders of glycosylation, however unsure whether this should be included on this panel.
Created: 25 Jan 2017, 11:34 a.m.

Emma Clement (Great Ormond Street Hospital)

I don't know

only 1 definite CMD case report but this group including DPM1-3 give overlap phenotype between CDG and CMD and it is probable that other CDG reports also have same muscle phenotype. Combined N and O glycolsylation defect so good molecular explanation, zebrs fish models show dystrophic muscle 4 biosynthetic pathways depend on DPM activity including O-mannosylation of ADG so good supportive data even if reported cases are few.
Created: 19 Dec 2016, 11:47 a.m.

Phenotypes
congenital muscular dystrophies

History Filter Activity

2 Jul 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: DPM1 were changed from congenital muscular dystrophies; Congenital disorder of glycosylation, type Ie 608799 to Congenital disorder of glycosylation, type Ie, OMIM:608799

2 Jul 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: DPM1 were set to 23109149; 23856421

2 Jul 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: DPM1.

29 Apr 2019, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene DPM1 were changed from 23856421; 23109149 to 23109149; 23856421

29 Apr 2019, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: DPM1 were set to 23856421 - an infant with the phenotype of a congenital muscular dystrophy, with borderline microcephaly, hypotonia, camptodactyly, severe motor delay, and elevated creatine kinase. Muscle biopsy showed muscular dystrophy and reduced α-dystroglycan immunostaining with glycoepitope-specific antibodies in a pattern diagnostic of dystroglycanopathy. The infant was compound heterozygous for a novel missense variant and an intragenic deletion from exons 3-7. In vitro studies showed decreased DPM1 activity in fibroblasts, and reduced binding to DPM3; 23109149 - DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies

29 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to DPM1.

29 Apr 2019, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source London South GLH was added to DPM1.

27 Jan 2017, Gel status: 2

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

27.01.2017 Panel revised after expert review and internal review with further curation.

27 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

27 Jan 2017, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for DPM1 was changed to BIALLELIC, autosomal or pseudoautosomal

27 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

25 Jan 2017, Gel status: 2

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for DPM1 were set to congenital muscular dystrophies;Congenital disorder of glycosylation, type Ie 608799

25 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

25 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

25 Jan 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for DPM1 were set to 23856421 - an infant with the phenotype of a congenital muscular dystrophy, with borderline microcephaly, hypotonia, camptodactyly, severe motor delay, and elevated creatine kinase. Muscle biopsy showed muscular dystrophy and reduced α-dystroglycan immunostaining with glycoepitope-specific antibodies in a pattern diagnostic of dystroglycanopathy. The infant was compound heterozygous for a novel missense variant and an intragenic deletion from exons 3-7. In vitro studies showed decreased DPM1 activity in fibroblasts, and reduced binding to DPM3; 23109149 - DPM2-CDG links the congenital disorders of glycosylation to the congenital muscular dystrophies

25 Jan 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for DPM1 were set to 23856421 - an infant with the phenotype of a congenital muscular dystrophy, with borderline microcephaly, hypotonia, camptodactyly, severe motor delay, and elevated creatine kinase. Muscle biopsy showed muscular dystrophy and reduced α-dystroglycan immunostaining with glycoepitope-specific antibodies in a pattern diagnostic of dystroglycanopathy. The infant was compound heterozygous for a novel missense variant and an intragenic deletion from exons 3-7. In vitro studies showed decreased DPM1 activity in fibroblasts, and reduced binding to DPM3.

19 Dec 2016, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DPM1 was added to Congenital muscular dystrophypanel. Source:

23 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DPM1 was added to Congenital muscular dystrophypanel. Sources: Emory Genetics Laboratory