"Our study represents the largest multicenter screening study for GlyT2 mutations in hyperekplexia to date," the authors wrote in their paper. They went on to say the work triples the number of known cases with these mutations, "firmly establishing mutations in the GlyT2 gene as a second major cause of startle disease."
In the other JBC paper, Beatriz Lpez-Corcuera at the Universidad Autnoma de Madrid in collaboration with Cecilio Gimnez and Pablo Lapunzinas groups at the IdiPAZ-Hospital Universitario La Paz and colleagues report another novel genetic mutation in GlyT2 as the cause of startle disease in eight patients from Spain and the United Kingdom.
Lpez-Corcuera said: "The mutation that we discovered is the first common dominant mutation in the GlyT2 gene," meaning that inheritance of a single defective copy of the gene causes disease.
The team found that the mutation hindered proper expression of the GlyT2 transporter at the cell membrane and changed how GlyT2 itself functions.
Lpez-Corcuera explains that this GlyT2 mutation reduces glycine uptake, which decreases the amount of glycine subsequently released and ultimately hinders transmission of the inhibitory signal. Lpez-Corcuera suggests that these results may explain the symptoms observed in the patients and "could be useful for future pharmacological approaches."
From the articles:
"A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2" by Cecilio Gimnez, Gonzalo Prez-Siles, Jaime Martnez- Villarreal, Esther Arribas-Gonzlez, Esperanza Jimnez, Enrique Nez, Jaime de Juan-Sanz, Enrique Fernndez-Snchez, Noem Garca-Tardn, Ignacio Ibez, Valeria Romanelli, Julin Nevado, Victoria M James, Maya Topf, Seo-Kyung Chung, Rhys H Thomas, Lourdes R Desviat, Carmen Aragn, Francisco Zafra, Mark I Rees, Pablo Lapunzina, Robert J Harvey, and Beatr
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