Novel THAP1 sequence variants in primary dystonia

Abstract

Background: THAP1 encodes a transcription factor (THAP1) that harbors an atypical zinc finger

The genetics of the dystonias – a review based on the new classification of the dystonias

“…Other studies, in contrast, have found a predominance of patients with focal dystonia 11,13 . One important finding is that most patients with focal dystonia have late-onset cervical dystonia 13 .…”

“…Other studies, in contrast, have found a predominance of patients with focal dystonia 11,13 . One important finding is that most patients with focal dystonia have late-onset cervical dystonia 13 . Since the first studies, it was observed that in patients with DYT6 dystonia, when the symptoms first appear in the limbs, they tend to predominate in the arms, unlike in DYT1 14,15 .…”

“…Adolescent-onset generalized dystonia followed by the segmental form is the most common presentation in most large series of DYT6 patients 12,13,14,15 . Other studies, in contrast, have found a predominance of patients with focal dystonia 11,13 .…”

Identification and functional analysis of novel THAP1 mutations

“…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.…”

“…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. [6][7][8][9][10][11][12][13][14][15] The phenotype though is highly variable even within a single family ranging from unaffected carriers to generalized dystonia.…”