Abstract

Combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA) is a devastating neurometabolic disorder, usually lethal in the first years of life. Autosomal recessive mutations in the SLC25A1 gene, which encodes the mitochondrial citrate carrier (CIC), were previously detected in patients affected with combined D/L-2-HGA. We showed that transfection of deficient fibroblasts with wild-type SLC25A1 restored citrate efflux and decreased intracellular 2-hydroxyglutarate levels, confirming that deficient CIC is the cause of D/L-2-HGA. We developed and implemented a functional assay and applied it to all 17 missense variants detected in a total of 26 CIC-deficient patients, including eight novel cases, showing reduced activities of varying degrees. In addition, we analyzed the importance of residues affected by these missense variants using our existing scoring system. This allowed not only a clinical and biochemical overview of the D/L-2-HGA patients but also phenotype-genotype correlation studies.

Autore Pugliese

• De Grassi Anna , Palmieri Luigi , Scarcia Pasquale , Porcelli Vito

Tutti gli autori

• DE GRASSI A.;PALMIERI F.;PALMIERI L.;SCARCIA P.;PORCELLI V.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2017

ISSN

0141-8955

ISBN

Non Disponibile

Numero di citazioni Wos

1

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

1

Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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