Limb-Girdle Muscular Dystrophy and Distal Myopathy
Gene: SQSTM1
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
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 listCreated: 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
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
Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
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