Dystonia - isolated/combined
Gene: RELN
Only identified a single proband with a rare de novo variant with a complex myoclonus-dystonia syndrome phenotype. Other study with segregation evidence, were missense variants that are too common in gnomAD v2.1
PMID: 32334381 - de novo c.6259T > C; W2087R. Male proband age of onset 26 yrs, with non progressive right upper limb dystonia, myoclonus, epilepsy, pyramidal syndrome, mild ID
PMID: 25648840 - 2 myoclonus-dystonia (MD) families segregating p.Thr1904Met (fam 1: 5 affected carriers & 5 unaffected non-carriers; fam 2: 5 affected carriers including obligates, 3 unaffected carriers, & 4 unaffected non-carriers). But, variant has 82 hets in gnomAD v2.1 (AF 0.03%) which is a bit high for a dominant condition. Another family segregating p.Ile1217Met with MD (3 affected carriers & 3 unaffected non carriers). However, there are 713 alleles in gnomAD v2.1 including 2 homozygotes (0.25% AF) which is too high for a dominant condition. 2 other missense reported in 2 MD probands, but both present in gnomAD v2.1 at frequencies not consistent with dominant disease.
Sources: OtherCreated: 23 Feb 2023, 3:56 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Myoclonus-dystonia syndrome MONDO:0000903
Publications
Gene: reln has been classified as Red List (Low Evidence).
gene: RELN was added gene: RELN was added to Dystonia - isolated/combined. Sources: Other Mode of inheritance for gene: RELN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RELN were set to 32334381; 25648840 Phenotypes for gene: RELN were set to Myoclonus-dystonia syndrome MONDO:0000903 Review for gene: RELN was set to RED