My friend BB alerted me to this study...
so, FYI,
http://www.ncbi.nlm.nih.gov/pmc/arti...4/?tool=pubmed
N Engl J Med. Author manuscript; available in PMC 2010 November 20.
Published in final edited form as:
N Engl J Med. 2010 May 20; 362(20): 1901–1908.
Published online 2010 May 5. doi: 10.1056/NEJMoa0907006
l-Histidine Decarboxylase and Tourette's Syndrome
A. Gulhan Ercan-Sencicek, Ph.D., Althea A. Stillman, Ph.D., Ananda K. Ghosh, Ph.D., Kaya Bilguvar, M.D., Brian J. O'Roak, Ph.D., Christopher E. Mason, Ph.D., Thomas Abbott, Abha Gupta, M.D., Ph.D., Robert A. King, M.D., David L. Pauls, Ph.D., Jay A. Tischfield, Ph.D., Gary A. Heiman, Ph.D., Harvey S. Singer, M.D., Donald L. Gilbert, M.D., Pieter J. Hoekstra, M.D., Ph.D., Thomas M. Morgan, M.D., Erin Loring, M.S., Katsuhito Yasuno, Ph.D., Thomas Fernandez, M.D., Stephan Sanders, M.D., Angeliki Louvi, Ph.D., Judy H. Cho, M.D., Shrikant Mane, Ph.D., Christopher M. Colangelo, Ph.D., Thomas Biederer, Ph.D., Richard P. Lifton, M.D., Ph.D., Murat Gunel, M.D., and Matthew W. State, M.D., Ph.D.
Quote:
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We have characterized a highly unusual two-generation pedigree in which Tourette's syndrome is segregated in an autosomal dominant fashion. Given that Tourette's syndrome has a population prevalence of 1% and a rate of recurrence of 10 to 15% among first-degree relatives of an affected person, it is extremely unlikely that all eight offspring of an affected parent would have Tourette's syndrome by chance, suggesting that this kindred indeed carries a mendelian form of the syndrome. The finding of a single segment of the genome that is shared among all affected members with a clearly deleterious mutation within this interval is also highly unlikely to occur by chance alone. Though the accepted standard for statistical significance on the basis of parametric linkage of a mendelian trait is a lod score of 3.0, these findings strongly point to a causal relationship between the identified mutation and Tourette's syndrome in this family.
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Very interesting to me indeed...
Edited to add after more research:
I found this in OMIM
http://omim.org/entry/142704#0001
after tracking an entry from
http://omim.org/entry/137580
Quote:
Molecular Genetics
Mutation in the HDC Gene
By genomewide linkage analysis followed by candidate gene sequencing in a large 2-generation family with Gilles de la Tourette syndrome, Ercan-Sencicek et al. (2010) identified a heterozygous nonsense mutation in the HDC gene (W317X; 142704.0001) in all 9 affected individuals. In vitro studies indicated that the mutation exerted a dominant-negative effect on the protein, resulting in lack of enzyme activity. Ercan-Sencicek et al. (2010) noted that animal studies had shown that lack of Hdc in mice results in increased locomotor and stereotypic behaviors, as well as increased anxiety. Overall, the findings suggested a role for histaminergic neurotransmission in neurobehavioral actions, such as tics.
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Quote:
.0001 GILLES DE LA TOURETTE SYNDROME
HDC, TRP317TER
In 9 affected members of a 2-generation family with Gilles de la Tourette syndrome (137580), Ercan-Sencicek et al. (2010) identified a heterozygous 951G-A transition in exon 9 of the HDC gene, resulting in a trp317-to-ter (W317X) substitution predicted to result in a truncated protein lacking key segments of the active domain. Studies of mRNA from patient cells suggested that the mutation escaped nonsense-mediated decay. The mutation was not found in 3,000 control chromosomes from northern and western Europe. In vitro studies in E. coli indicated that the mutant protein acted in a dominant-negative manner, resulting in lack of enzyme activity. All 9 affected individuals had Tourette syndrome, 4 also had obsessive-compulsive disorder (OCD; 164230), and 1 also had Asperger syndrome (see 608638).
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