RT Journal Article
T1 A new seipin-associated neurodegenerative syndrome
A1 Sánchez Iglesias, Sofía
A1 Ruibal, Álvaro
A1 Rodríguez Requena, Jesús
A1 Araujo-Vilar, David
A1 Guillén-Navarro, Encarna
A1 Domingo-Jiménez, Rosario
A1 Victoria Martínez, Berta
A1 Ruiz Riquelme, Alejandro Iván
A1 Rábano, Alberto
A1 Loidi, Lourdes
A1 Beiras-Iglesias, Andrés
A1 González Méndez, Blanca
A1 Ramos, Adriana
A1 López González, Vanesa
A1 Ballesta Martinez, Maria Juliana
A1 Garrido Pumar, Miguel
A1 Aguiar, Pablo
K1 Seipin/BSCL2 mutations
K1 Neurodegenerative syndrome
AB Background: Seipin/BSCL2 mutations can cause type2 congenital generalised lipodystrophy (BSCL) ordominant motor neurone diseases. Type 2 BSCL isfrequently associated with some degree of intellectualimpairment, but not to fatal neurodegeneration. In orderto unveil the aetiology and pathogenetic mechanisms ofa new neurodegenerative syndrome associated with anovel BSCL2 mutation, six children, four of themshowing the BSCL features, were studied.Methods: Mutational and splicing analyses of BSCL2were performed. The brain of two of these children wasexamined postmortem. Relative expression of BSCL2transcripts was analysed by real-time reversetranscription-polymerase chain reaction (RT-PCR) indifferent tissues of the index case and controls.Overexpressed mutated seipin in HeLa cells was analysedby immunofluorescence and western blotting.Results: Two patients carried a novel homozygousc.985C>T mutation, which appeared in the other fourpatients in compound heterozygosity. Splicing analysisshowed that the c.985C>T mutation causes an aberrantsplicing site leading to skipping of exon 7. Expression ofexon 7-skipping transcripts was very high with respect tothat of the non-skipped transcripts in all the analysedtissues of the index case. Neuropathological studiesshowed severe neurone loss, astrogliosis and intranuclearubiquitin(+) aggregates in neurones from multiplecortical regions and in the caudate nucleus.Conclusions: Our results suggest that exon 7 skippingin the BSCL2 gene due to the c.985C>T mutation isresponsible for a novel early onset, fatalneurodegenerative syndrome involving cerebral cortexand basal ganglia.
PB BMJ Publishing Group
SN 0022-2593
YR 2013
FD 2013
LK http://hdl.handle.net/10347/32442
UL http://hdl.handle.net/10347/32442
LA eng
NO Guillén-Navarro E, Sánchez-Iglesias S, Domingo-Jiménez R, et alA new seipin-associated neurodegenerative syndromeJournal of Medical Genetics 2013;50:401-409.
NO Instituto de Salud Carlos III (grant number PI 10/02873) and EuropeanRegional Development Fund, FEDER (grant number 10PXIB208013PR) andConsellería de Industria, Xunta de Galicia.
DS Minerva
RD 29 abr 2026