Intellectual disability syndromic and non-syndromic
Gene: DAG1

DAG1 (dystroglycan 1)
EnsemblGeneIds (GRCh38): ENSG00000173402
EnsemblGeneIds (GRCh37): ENSG00000173402
OMIM: 128239, Gene2Phenotype
DAG1 is in 12 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Bi-allelic variants in this gene are associated with a range of dystroglycanopathy phenotypes on a spectrum from isolated muscle disease through to severe brain malformations together with muscle disease. ID is part of the phenotypic spectrum of the more severely affected individuals.
Created: 5 Dec 2022, 4:21 a.m. | Last Modified: 5 Dec 2022, 4:21 a.m.

Panel Version: 0.5067

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9

Created: 5 Dec 2022, 4:21 a.m.
Last Modified: 5 Dec 2022, 4:21 a.m.
Panel version: 0.5067

Nicholas Clark (Other)

I don't know

Three homozygotes for the NM_004393.4(DAG1):c.743del p.(Ala248Glufs*19) variant were identified in a consanguineous family. All presented with hydrocephalus. One of these individuals was described as having "severe brain malformations" and the only survivor of the three at time of publication was described as having "profound intellectual disability". Two siblings who were homozygous for the NM_004393.4(DAG1):c.2006G>T p.(Cys669Phe) variant have been reported to have intellectual disability. An individual with cognitive impairment has been reported to be homozygous for the NM_004393.4(DAG1):c.575C>T p.(Thr192Met) variant. Two siblings from a consanguineous family who were reported to have muscular dystrophy-dystroglycanopathy were homozygous for the NM_004393.4(DAG1):c.2326C>T p.(Arg776Cys) variant but were not reported to have intellectual disability. Another individual with dystroglycanopathy who was reported to be compound heterozygous for the NM_004393.4(DAG1):c.222G>A p.(Val74Ile) and the NM_004393.4(DAG1):c.331G>A p.(Asp111Asn) variants was also not reported to have intellectual disability.

Mouse models have indicated that a lack of dystroglycan can result in brain malformations.
Created: 4 Dec 2022, 10:48 p.m. | Last Modified: 4 Dec 2022, 10:48 p.m.

Panel Version: 0.5067

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9

Publications

Created: 4 Dec 2022, 10:48 p.m.
Last Modified: 4 Dec 2022, 10:48 p.m.
Panel version: 0.5067

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9

OMIM

128239

Clinvar variants

Variants in DAG1

Penetrance

None

Publications

Panels with this gene