Singular DYT6 phenotypes in association with new THAP1 frameshift mutations

Abstract

International audienc

Identification and functional analysis of novel THAP1 mutations

“…About 50 different THAP1 mutations have been reported to date. 2,[6][7][8][9][10][11][12][13][14][15][16][17]22 One-third of the mutations represents missense mutations located in the THAP domain and is thought to interrupt DNA binding. Another one-third of the mutations are considered to disturb the NLS, such as nonsense mutations, small insertions/deletions, or missense mutations within the NLS.…”

“…5 About 50 different THAP1 mutations have been reported to date including missense, nonsense, and frameshift mutations. 2,[6][7][8][9][10][11][12][13][14][15][16][17] In addition to the disease-causing mutations, two variants, c.-237_236delinsTT and c.71+9C4A, in the non-coding region of THAP1 may be associated with dystonia. 9,13 DYT6 typically manifests as early-onset generalized or segmental dystonia, frequently with prominent laryngeal involvement and a rostrocaudal evolution of symptoms.…”

DYT6 dystonia: Review of the literature and creation of the UMD locus-specific database (LSDB) for mutations in the THAP1 gene

“…Several teams have reported to date 53 different mutations in the coding sequence of THAP1 in 56 families (56 probands and 43 relatives) of American Xiao et al, 2010], Chinese [Cheng et al, 2010;Xiao et al, 2010], Czech [Jech et al, 2011], Dutch [Groen et al, 2010], English [Houlden et al, 2010], French [Blanchard et al, 2011;Clot et al, 2010;Houlden et al, 2010] Gavarini et al, 2010;Kaiser et al, 2010] and insufficient clinical and molecular data for 10 relatives do not allow to implement them in the database . One of the mutation has been described in an asymptomatic individual control (c.197_198delAG) [Söhn et al, 2010].…”

“…This insertion is predicted to create a premature termination codon (PTC), codon seven amino acids downstream of the mutation (position 178) [Blanchard et al, 2011].…”

Inherited Isolated Dystonia: Clinical Genetics and Gene Function

“…In this report, the Amish-Mennonite population were found to have an insertiondeletion ("indel") mutation and a German family was found to have a missense mutation (F81L) that appeared to impair DNA binding. Subsequently, a large number of different mutations in THAP1 have been identified in a wide range of ethnicities [33][34][35][36][37], linking this gene to a far larger number of inherited cases of dystonia than had been suspected previously. The number of reported mutations led to the creation of a locus-specific database (http://www.umd.be/THAP1/{Blanchard), which by 2011 already included 56 different families, most of which have unique mutations.…”