Dystonia - isolated/combined

Gene: COL6A3

I don't know

PMID: 32037012 - Panda and Sharawat 2020 - report a new case of COL6A3 mutation associated early-onset isolated dystonia-DYT27 in an 8 year old boy. Compound heterozygous variants in exons 10 and 12 found (p.Gly1517Ser and p.Pro1894Leu).

Created: 5 Sep 2020, 4:45 a.m. | Last Modified: 5 Sep 2020, 4:45 a.m.

Panel Version: 0.15

Three unrelated German families reported initially. Onset of segmental isolated dystonia involving the face, neck, bulbar muscles, and upper limbs at age 20 years. All patients carried mutations affecting the C terminus, with at least 1 mutation specifically affecting exon 41. Note recent report of bi-allelic variants in exon 10 and 12 however (PMID: 32037012) and also PMID: 26872670 which calls into question this gene-disease association, due in part to presence of two homozygotes for the p.Pro3082Arg variant in gnomad.

Created: 28 Mar 2020, 9:51 p.m. | Last Modified: 28 Mar 2020, 9:51 p.m.

Panel Version: 0.27

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dystonia 27, MIM#616411

Publications

• 26004199
• 32037012
• 26872670
• 32037012

Green List (high evidence)

Genotype-phenotype correlation:
1. Bethlem myopathy: AR is more severe and caused by LoF; AD is milder and caused by inframe exon skipping variants and glycine substitutions. (PMID: 20301676);
2. Ullrich: AR is caused by NMD, ss leading to inframe del or normal inframe del. AD is milder and caused by glycine substitutions. AD is also caused by inframe exon del (caused by ss) and normal inframe del that preserve a unique cysteine important for dimer formation. (PMID: 20301676)
*Bethlem and Ullrich are overlapping
3. Dystonia: 3 German families studied, all dystonia patients had at least one variant in exon 41 (C-terminal), while myopathies cluster in the N-terminal. Only biallelic patients reported (PMID: 26004199)

Created: 27 Mar 2020, 6:30 a.m. | Last Modified: 27 Mar 2020, 6:30 a.m.

Panel Version: 0.20

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Bethlem myopathy 1, 158810 AD, AR; Dystonia 27, 616411 AR; Ullrich congenital muscular dystrophy 1, 254090 AD, AR

Publications

• 20301676
• 26004199