Haplotype analysis at the DYT1 Locus in ashkenazi jewish patients with occupational hand dystonia

Abstract

Genetic haplotypes at five marker loci that are closely linked to the DYT1 gene on chromosome 9q were determined in 10 Ashkenazi Jewish patients with focal hand dystonia (eight with musician's cramp, two with writer's cramp). The founder haplotype associated with > 90% of cases generalized dystonia in the Ashkenazi Jewish population could not be constructed from any of the twenty chromosomes. Potential haplotypes were determined, and no common haplotype was discerned in these patients. These findings argue against a role for the founder mutation in the DYT1 gene in the etiology of occupational hand dystonia in this ethnic group. Further, if the DYT1 gene is involved in these later onset dystonias, there is no evidence for a common mutation in the Ashkenazic Jewish population. It appears that excessive, repetitive use, possibly in combination with ulnar neuropathy, may serve as the inciting cause of some focal dystonias.

TheDYT1 GAG deletion is infrequent in sporadic and familial writer's cramp

“…This mutation was not found in any of our 44 index cases. Even taking into account the possibility that the only mutation carrier we identified might have presented as an index patient, this indicates, in accordance with previous findings in Ashkenazi Jewish patients, 10 that the overall frequency of mutation carriers in cases of writer's cramp is low (<3%). Thus, it appears that isolated unilateral or bilateral writer's cramp, whether familial or sporadic, is only rarely a phenotypic manifestation of the DYT1 GAG deletion.…”

Movement dysfunction following repetitive hand opening and closing: Anatomical analysis in owl monkeys

“…[1][2][3][4] There may be different types of focal hand dystonia arising from a variety of independent or interacting factors including genetics, dopamine deficiency, ulnar neuropathy, drugs, basal ganglia disease, trauma, head injury, chronic pain, or stereotypical task repetition. 1,3,[17][18][19][20][21][22][23][24][25][26][27][28] Hand dystonia is persistent and difficult to treat. 29 Normal hand control rarely returns spontaneously even when an individual stops doing the target task, takes time off work, rests the hand, takes muscle relaxants or anti-inflammatories, or is injected with botulinum toxin.…”

Learning-based Animal Models: Task-specific Focal Hand Dystonia

“…• genetics (Gasser et al 1996;Illarioshkin et al 1988;Leube et al 1996;Ozelius et al 1997); • an imbalance of inhibitory and excitatory pathways in the globus pallidus or substantia nigra (Black et al 1998;DeLong 1990;DeLong et al 1985;Perlmutter et al 1997); • cortical dysfunction (Chase et al 1988;Defendini and Fahn 1988;Deuschl et al 1995;Gilman et al 1988;Tempel and Perlmutter 1993;Toro et al 2000); • degradation of somatotopic representations in the thalamus (Lenz and Byl 1999;Uitti et al 1995;Zirh et al 1998); • disruption of sensory perception, somatosensory representation, and/or cortical sensory activation (BaraJimenez et al 1998(BaraJimenez et al , 2000Butterworth et al 2003;Byl and Topp 1998;Byl et al 1996aByl et al ,b,c, 1997Byl et al , 2000aByl et al ,b,c, 2002Chen and Hallett 1998;McKenzie et al 2003;Tinazzi et al 1999Tinazzi et al , 2003; • abnormal presynaptic desynchronization of movement or abnormal muscle spindle afferent firing (Grunewald et al 1997;Toro et al 2000); • abnormal gating of somatosensory inputs (Murase et al 2000); • disruption of inhibition in the spinal cord (Chen et al 1995;Kaji et al 1995;Nakashima et al 1989;Naumann and Reiners ...…”