Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: SQSTM1

Amber List (moderate evidence)

SQSTM1 (sequestosome 1)
EnsemblGeneIds (GRCh38): ENSG00000161011
EnsemblGeneIds (GRCh37): ENSG00000161011
OMIM: 601530, Gene2Phenotype
SQSTM1 is in 11 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

I don't know

5 unrelated probands with adult-onset myopathy with a SQSTM1 variant (2 with c.1165+1G>A & 3 with p.Pro392Leu) that also co-occurred with TIA1 p.Asn357Ser. Also experimental evidence that presence of TIA1 variant is required along with a SQSTM1 variant for the myodegenerative phenotype. The p.Pro392Leu variant previously reported as pathogenic has 255 hets & 2 homozygotes in gnomAD v2.1, which is common for a dominant disease but could support the digenic inheritance of the myopathy.
Created: 28 Apr 2021, 2:23 a.m. | Last Modified: 28 Apr 2021, 2:23 a.m.
Panel Version: 0.105

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, distal, with rimmed vacuoles, MIM#617158; myofibrillar myopathy

Publications

Elena Savva (Victorian Clinical Genetics Services)

Red List (low evidence)

PMID: 27545679 - 9 patients (4 families) with childhood/adolescent onset neurodegeneration syndrome. 7/9 patients presented with dystonia. Cerebellar atrophy also reported in 4/8 patients, none noted to have myopathy.

PMID: 26208961 - 2 families (3 patients) with lower limb weakness with rimmed vacuoles upon muscle biopsy. Onset in both families was ~50 years old, and both were heterozygous for splice variant c.1165+1G>A - proven to result in both a PTC and inframe deletion.

Summary - Single report of myopathy and none had paediatric onset.
Sources: Expert list
Created: 22 Jun 2020, 3:10 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Myopathy, distal, with rimmed vacuoles 617158

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Nine individuals from four unrelated families.
Created: 17 Apr 2020, 12:12 a.m. | Last Modified: 13 Sep 2020, 6:52 a.m.
Panel Version: 0.4395

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, MIM# 617145

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
  • Expert list
  • Royal Melbourne Hospital
  • Victorian Clinical Genetics Services
Phenotypes
  • myopathy, distal, with rimmed vacuoles MONDO:0014945
  • multisystem proteinopathy
OMIM
601530
Clinvar variants
Variants in SQSTM1
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: sqstm1 has been classified as Amber List (Moderate Evidence).

17 Apr 2023, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: sqstm1 has been classified as Amber List (Moderate Evidence).

14 Apr 2023, Gel status: 1

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

Bryony Thompson (Royal Melbourne Hospital)

gene: SQSTM1 was added gene: SQSTM1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Literature Mode of inheritance for gene: SQSTM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SQSTM1 were set to 29599744; 26208961; 29457785 Phenotypes for gene: SQSTM1 were set to myopathy, distal, with rimmed vacuoles MONDO:0014945; multisystem proteinopathy Mode of pathogenicity for gene: SQSTM1 was set to Other