RT Journal Article
T1 Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant
A1 Sánchez Iglesias, Sofía
A1 Crocker, Melissa
A1 O'Callaghan, Mar
A1 Darling, Alejandra
A1 García-Cazorla, Angels
A1 Domingo-Jiménez, Rosario
A1 Castro, Ana
A1 Fernández-Pombo, Antía
A1 Ruibal, Álvaro
A1 Aguiar, Pablo
A1 Garrido Pumar, Miguel
A1 Rodríguez Núñez, Antonio
A1 Álvarez Escudero, Julián
A1 Brown, Rebecca
A1 Araujo-Vilar, David
AB Celia’s encephalopathy (progressive encephalopathy with/without lipodystrophy (PELD)) is a childhood neurodegenerative disorder with a fatal prognosis before the age of 10, due to the variant c.985C>T in the BSCL2 gene that causes a cryptic splicing site leading to skipping of exon 7. For years, different authors have reported cases of congenital generalized lipodystrophy due to the variant c.974dupG in BSCL2 associated with neurological manifestations of variable severity, although some of them clearly superimposable to PELD. To identify the molecular mechanisms responsible for these neurological alterations in two patients with c.974dupG. Clinical characterization, biochemistry, and neuroimaging studies of two girls carrying this variant. In silico analysis, PCR amplification, and BSCL2 cDNA sequencing. BSCL2-201 transcript expression, which lacks exon 7, by qPCR in fibroblasts from the index case, from a healthy child as a control and from two patients with PELD, and in leukocytes from the index case and her parents. One with a severe encephalopathy including a picture of intellectual deficiency, severe language impairment, myoclonic epilepsy, and lipodystrophy as described in PELD, dying at 9 years and 9 months of age. The other 2-year-old patient showed incipient signs of neurological involvement. In silico and cDNA sequencing studies showed that variant c.974dupG gives rise to skipping of exon 7. The expression of BSCL2-201 in fibroblasts was significantly higher in the index case than in the healthy child, although less than in the case with homozygous PELD due to c.985C>T variant. The expression of this transcript was approximately half in the healthy carrier parents of this patient. The c.974dupG variant leads to the skipping of exon 7 of the BSCL2 gene and is responsible for a variant of Celia’s encephalopathy, with variable phenotypic expression.
PB Springer
YR 2019
FD 2019
LK http://hdl.handle.net/10347/32473
UL http://hdl.handle.net/10347/32473
LA eng
NO Sánchez-Iglesias, S., Crocker, M., O’Callaghan, M. et al. Celia’s encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant. Neurogenetics 20, 73–82 (2019). https://doi.org/10.1007/s10048-019-00574-5
NO This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s10048-019-00574-5
DS Minerva
RD 26 abr 2026