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Gilles de la Tourette’s syndrome
Published in David Enoch, Basant K. Puri, Hadrian Ball, Uncommon Psychiatric Syndromes, 2020
David Enoch, Basant K. Puri, Hadrian Ball
There is also some evidence of an association with glutamatergic-related neurotransmission genes. The E219D allele, a missense variant, of the glial high affinity glutamate transporter gene EAAT1 (or SLC1A3), located at 5p13.2, has been reported to be 2.4 times higher (though not conventionally statistically significantly higher; p = 0.09) in a Tourette syndrome cohort compared with controls (Adamczyk et al., 2011). Non-significant (after correcting for multiple testing) associations with Tourette syndrome were also reported in the same year in respect of SAPAP3/DLGAP3 (SAP90/PSD95-associated protein 3; a post-synaptic scaffolding protein which is highly expressed in striatal glutamatergic synapses), located at 1p34.3, for the SNP rs11264126 and two haplotypes containing rs11264126 and rs12141243 (Crane et al., 2011).
Migraine pathways and the identification of novel therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2020
Innocenzo Rainero, Fausto Roveta, Alessandro Vacca, Cecilia Noviello, Elisa Rubino
In the last two decades, molecular genetic studies have provided considerable insights into the molecular mechanisms of migraine, suggesting new therapeutic targets. First of all, Familial Hemiplegic Migraine (FHM), a rare MA subtype characterized by an autosomal dominant transmission of the phenotype and presence of transient motor deficits, has been associated with mutations in three different genes, CACNA1A, ATP1A2, and SCN1A, coding for protein linked to ion channels functions [44–46]. In addition, investigating families with rare, monogenic forms of migraine, pathogenic variants in other genes, as KCNK18, PRRT2, PNKD, SLC2A1, SLC1A3, and SLC4A4 have been demonstrated [47,48]. In the more common form of migraine, candidate gene association studies showed that more than 200 genetic variants in approximately 100 different genes may be associated or influence the clinical characteristics of the disease [49]. However, these studies often report conflicting results and have been rarely replicated. Finally, several genome-wide association studies (GWAS) provided evidence that numerous single-nucleotide polymorphisms (SNPs), and related genes, are significantly associated with migraine and its clinical variants. The most recent meta-analysis combined the data from 22 GWAS, comprising 59,674 migraine cases from clinic- and population-based collections as well as 316,078 controls [50]. This study demonstrated that 44 independent SNPs at 38 distinct genomic loci are significantly associated with migraine, providing new molecular insight into the molecular pathways of migraine.
Brain Gene Expression Profiling of Individuals With Dual Diagnosis Who Died by Suicide
Published in Journal of Dual Diagnosis, 2020
Brenda Cabrera-Mendoza, Cristóbal Fresno, Nancy Monroy-Jaramillo, Gabriel Rodrigo Fries, Consuelo Walss-Bass, David C. Glahn, Patricia Ostrosky-Wegman, Alma Delia Genis-Mendoza, José Jaime Martínez-Magaña, Ana Luisa Romero-Pimentel, Carlos Enrique Díaz-Otañez, Fernando García-Dolores, Eli Elier González-Sáenz, Roberto Cuauhtemoc Mendoza-Morales, Gonzalo Flores, Rubén Vázquez-Roque, Humberto Nicolini
Besides gene expression changes in biological pathways similar to the previous comparison, such as synaptic signaling, a differential expression of genes involved in GABAergic and glutamatergic neurotransmission was detected between suicides with DD and suicides with MD. The upregulation of the glutamate transporter SLC1A3 is remarkable, as the downregulation of this gene has been reported in persons with MD (Choudary et al., 2005; Sequeira et al., 2009). These could be a pivotal difference between patients with DD and patients with MD and might underlie the poor prognosis associated with patients with DD in comparison with those with MD.
Paroxysmal movement disorders – practical update on diagnosis and management
Published in Expert Review of Neurotherapeutics, 2019
Claudio M. De Gusmao, Laura Silveira-Moriyama
In 1946, while working at the Mayo clinic, Parker observed a series of 11 cases in which patients had abrupt, recurrent attacks of cerebellar dysfunction with nystagmus. Several cases were diagnosed with multiple sclerosis, but he noted that four individuals did not have the usual features of typical MS and bore a positive family history, coining the syndrome ‘periodic ataxia’ [12,13]. In the ensuing decades, awareness of the condition increased when unrelated kindreds were reported noting autosomal dominant inheritance and a gamut of different symptoms: heterogeneous attacks combining ataxia, dysarthria, nystagmus and vertigo, with variable duration and triggered by alcohol, fatigue and emotional stress; interictal nystagmus, myokymia or carpopedal spasms [14–20]. The serendipitous discovery of acetazolamide [19]responsiveness helped further efforts to classify subtypes of periodic ataxia. Until the 1980s variable terms such as ‘periodic ataxia’ or ‘paroxysmal ataxia’ were used. The header ‘episodic ataxia’ (EA) was later consolidated after a landmark paper by Gancher and Nutt in 1986 describing six kindreds (including one family with 26 members examined) in which the authors distinguished three different syndromes: episodic ataxia with interictal neuromyotonia and positive response to phenytoin (later named episodic ataxia type 1), episodic ataxia with interictal nystagmus which often responded to acetazolamide (later named episodic ataxia type 2) and a third type with combined periodic ataxias and dyskinesias with kinesigenic triggers [21]. In the following decade, various linkage analyses studies linked different kindreds and their specific phenotypes to different loci, creating the current nomenclature of EA1, EA2, EA3, etc. In four of these loci, genes relating to transmembrane proteins have been identified: KCNA1 for EA1, CACNA1A for EA2, CACNB4 for EA5 and SLC1A3 for EA6.