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www.ciberer.es

• h-b Mb, s s, o iJ, F i, h s, a M, G k, V
Most relevant oeGGeileririsirozcoerrerohenseeubersonöddeilches
c, lóPez de heredia M, nunes V*, estéVez r*, Jenstch tJ*. Disrupting MLC1 and GlialCAM
scientific and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction

articles
Nature communications DOI:10.1038/ncomms4475 (2014).

• caPdeVila-nortes X, lóPez-hernández t, aPaJa PM, lóPez de heredia M, sirisi s. calleJo G,

arnedo t, nunes V, lukacs Gl, Gasull X, estéVez r. Insights into MLC pathogenesis:
GlialCAM is an MLC1 chaperone required for proper activation of volume-regulated

anion currents. Hum Mol Gen 22: 4405-16 (2013).

• Van der knaaP Ms, boor i, estéVez r. Megalencephalic leukoencephalopathy with
subcortical cysts: chronic white matter oedema due to a defect in brain ion and

water homeostasis. Lancet Neurol 11: 973-85 (2012).

• JeWorutzki e, lóPez-hernández t, caPdeVila-nortes X, sirisi s, benGtsson l, Montolio M,
z G, a t, M cs, s u, n V, M a, J tJ, G X,
iFarellirnedoüllerchulteunesartínezentschasulló
Pusch M, estéVez r. GlialCAM, a protein defective in a leukodystrophy, serves as

a ClC-2 Cl(-) channel auxiliary subunit. Neuron 73: 951-61 (2012). Comment in
Neuron (2012), 73.

• lPez-hernández t, ridder Mc, Montolio M, caPdeVila-nortez X, Polder e, sirisi s, duarri

a, schulte u, Fakler b, nunes V, schePer Gc, Martínez a, estéVez r*, Van der knaaP Ms*.
GlialCAM mutations cause megalencephalic leukoencephalopathy with subcortical

cysts, and also benign familial macrocephaly and macrocephaly with retardation and
autism. Am J Hum Genetics, 88:422-32 (2011) Comment in Am J Hum Gen (2011).

Highlights
In this year 2013 our group has made progress in the understanding of the mo-
lecular basis of the rare disease megalencephalic leukoencephalopathy (Known

as MLC). Previous of our group have identified the second disease gene, which
is called GLIALCAM. During this year, we have been able to understand the bio-

chemical relationship between the two proteins involved in the disease. We have

also generated and studied KO animal models in mice and zebrafish. The studies ç
of these models have allowed clarifying the fact that MLC patients with mutations

in MLC1 or GLIALCAM share the same clinical symptoms. These models could be
í
used in a near future to develop new therapies for patients with MLC.

During 2013, our group obtained funding from European Leukodystrophy Asso-
ciation (ELA) for the project MLC disease: indentification of proteins which could

modulate the disease phenotype, from Ministerio de Economía y competitividad
(MCOC) for the project Subunidades reguladoras de canales de CI-CLC y sus

enfermedades asociadas Leucoencefalopata megalencefálica y síndrome de Bar-

tter, and from AFM (Assocation Franaise contre les myopathies) for the project
Development and characterization of a zebrafish model of myotonia congénita. In

general, our group is studying rare genetic diseases caused by defects in chloride
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channels.
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