Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: DNMT3B

Amber List (moderate evidence)

DNMT3B (DNA methyltransferase 3 beta)
EnsemblGeneIds (GRCh38): ENSG00000088305
EnsemblGeneIds (GRCh37): ENSG00000088305
OMIM: 602900, Gene2Phenotype
DNMT3B is in 14 panels

2 reviews

Bryony Thompson (Royal Melbourne Hospital)

I don't know

FSHD shares some features with LGMD.
Two families reported with FSHD2. In one family carriers of the heterozygous DNMT3B missense variant (c.1579T>C) had reduced DNA methylation levels at the D4Z4 repeat array and were more likely to develop FSHD in comparison to other family members carrying an identical permissive 4qA allele of 9 D4Z4 units. In the other family, digenic inheritance of a heterozygous DNMT3B missense variant (c.2072C>T) and a permissive 4qA allele of 13 D4Z4 units induced hypomethylation at the D4Z4 repeat array but only one of the two family members was diagnosed with FSHD. A mouse model with an in-frame deletion (similar to the reported missense variants) does not induce a skeletal muscle pathology nor does it increase the extremely low DUX4 transcript levels in skeletal muscles of a FSHD transgenic mouse. The mouse model also suggested that Smchd1 may have a more potent role in DUX4 derepression than Dnmt3b.
Sources: Literature
Created: 6 Jun 2022, 2:01 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Facioscapulohumeral muscular dystrophy MONDO:0001347

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Well-established disease-gene association; more than 20 unrelated individuals; three mouse models Homozygous and compound heterozygous missense, nonsense, splice-site (leading to 3aa insertion) result in LOF disease mechanism. Individuals typically presented with immunodeficiencies (decreased immunoglobulin production, low T/B/NK cells), centric instability, facial anomalies and recurrent respiratory infections; however, severity varies.
Created: 27 Jul 2021, 6:39 a.m. | Last Modified: 27 Jul 2021, 6:39 a.m.
Panel Version: 0.8524

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency-centromeric instability-facial anomalies syndrome 1 MIM# 242860; facial dysmorphic features; flat nasal bridge; developmental delay; macroglossia; bacterial/opportunistic infections (recurrent); malabsorption; cytopaenia; malignancies; multiradial configurations of chromosomes 1, 9, 16; Hypogammaglobulinaemia; agammaglobulinaemia; variable antibody deficiency; decreased immunoglobulin production; low T/B/NK cells

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Facioscapulohumeral muscular dystrophy MONDO:0001347
OMIM
602900
Clinvar variants
Variants in DNMT3B
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Jun 2022, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: dnmt3b has been classified as Amber List (Moderate Evidence).

6 Jun 2022, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: dnmt3b has been classified as Amber List (Moderate Evidence).

6 Jun 2022, Gel status: 1

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

Bryony Thompson (Royal Melbourne Hospital)

gene: DNMT3B was added gene: DNMT3B was added to Limb Girdle Muscular Dystrophy. Sources: Literature Mode of inheritance for gene: DNMT3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DNMT3B were set to 27153398; 33004076 Phenotypes for gene: DNMT3B were set to Facioscapulohumeral muscular dystrophy MONDO:0001347 Review for gene: DNMT3B was set to AMBER