Muscular dystrophy and myopathy_Paediatric

Gene: DTNA

Green List (high evidence)

DTNA (dystrobrevin alpha)
EnsemblGeneIds (GRCh38): ENSG00000134769
EnsemblGeneIds (GRCh37): ENSG00000134769
OMIM: 601239, Gene2Phenotype
DTNA is in 6 panels

1 review

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

12 individuals from 4 unrelated families with 2 different monoallelic DTNA variants in exon 18 and affecting the coiled-coil domain of α-dystrobrevin (DTNA). DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype.

Clinical features with onset between 1st and 4th decades included: myalgia, muscle cramps associated with physical activity, exercise intolerance, and increased serum CK (11/12). Most patients have mild symptoms, only 3 had mild proximal muscle weakness of the lower limbs, and 1 had episode of rhabdomyolysis @20yrs. Muscle biopsies in 8 individuals showed mild myopathic and/or dystrophic features.

The 2 variants (p.Glu529Lys and p.Gln523_Glu529del) were found by targeted exome sequencing and confirmed by Sanger sequencing. They segregated with the disorder in the families and were absent in gnomAD. Immunofluorescent analysis of patient muscle samples showed decreased DTNA immunoreactivity at the sarcolemma, as well as variably reduced immunoreactivity of several other dystrophin-glycoprotein complex (DGC) proteins, suggesting that the DTNA variants resulted in overall destabilization of the DG complex within skeletal muscle.
Sources: Literature
Created: 7 Nov 2024, 2:04 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Muscular dystrophy, MONDO:0020121, DTNA-related
OMIM
601239
Clinvar variants
Variants in DTNA
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

8 Nov 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: dtna has been classified as Green List (High Evidence).

8 Nov 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: DTNA were changed from Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322 to Muscular dystrophy, MONDO:0020121, DTNA-related

7 Nov 2024, Gel status: 3

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: dtna has been classified as Green List (High Evidence).

7 Nov 2024, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Chirag Patel (Genetic Health Queensland)

gene: DTNA was added gene: DTNA was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature Mode of inheritance for gene: DTNA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DTNA were set to PMID: 36799992 Phenotypes for gene: DTNA were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis MONDO:0859322 Mode of pathogenicity for gene: DTNA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: DTNA was set to GREEN