02656nas a2200421 4500008004100000022001400041245010400055210006900159260001700228300000900245490000800254520136600262653001501628653001001643653003201653653001001685653001001695653001101705653004201716653001101758653001101769653000901780653003001789653001301819100001901832700003401851700002701885700002601912700002801938700002301966700001901989700002902008700002002037700001702057700001802074700001902092856012302111 2013 eng d a1096-720600aExome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.0 aExome sequencing identifies a new mutation in SERAC1 in a patien c2013 Sep-Oct a73-70 v1103 a
3-Methylglutaconic aciduria (3-MGA-uria) is a heterogeneous group of syndromes characterized by an increased excretion of 3-methylglutaconic and 3-methylglutaric acids. Five types of 3-MGA-uria (I to V) with different clinical presentations have been described. Causative mutations in TAZ, OPA3, DNAJC19, ATP12, ATP5E, and TMEM70 have been identified. After excluding the known genetic causes of 3-MGA-uria we used exome sequencing to investigate a patient with Leigh syndrome and 3-MGA-uria. We identified a homozygous variant in SERAC1 (c.202C>T; p.Arg68*), that generates a premature stop codon at position 68 of SERAC1 protein. Western blot analysis in patient's fibroblasts showed a complete absence of SERAC1 that was consistent with the prediction of a truncated protein and supports the pathogenic role of the mutation. During the course of this project a parallel study identified mutations in SERAC1 as the genetic cause of the disease in 15 patients with MEGDEL syndrome, which was compatible with the clinical and biochemical phenotypes of the patient described here. In addition, our patient developed microcephaly and optic atrophy, two features not previously reported in MEGDEL syndrome. We highlight the usefulness of exome sequencing to reveal the genetic bases of human rare diseases even if only one affected individual is available.
10aAdolescent10aAdult10aCarboxylic Ester Hydrolases10aChild10aExome10aFemale10aHigh-Throughput Nucleotide Sequencing10aHumans10aInfant10aMale10aMetabolism, Inborn Errors10amutation1 aTort, Frederic1 aGarcía-Silva, María, Teresa1 aFerrer-Cortès, Xènia1 aNavarro-Sastre, Aleix1 aGarcia-Villoria, Judith1 aColl, Maria, Josep1 aVidal, Enrique1 aJiménez-Almazán, Jorge1 aDopazo, Joaquin1 aBriones, Paz1 aElpeleg, Orly1 aRibes, Antonia uhttps://clinbioinfosspa.es/content/exome-sequencing-identifies-new-mutation-serac1-patient-3-methylglutaconic-aciduria