Biallelic mutations in NDUFAF6 have been identified as responsible for cases of autosomal recessive Leigh syndrome associated with mitochondrial complex I deficiency. Here we report two siblings and two unrelated subjects with Leigh syndrome, in which we found the same compound heterozygous missense (c.532G>C:p.A178P) and deep intronic (c.420+784C>T) variants in NDUFAF6. We demonstrated that the identified intronic variant creates an alternative splice site, leading to the production of an aberrant transcript. A detailed analysis of whole-exome sequencing data together with the functional validation based on mRNA analysis may reveal pathogenic variants even in non-exonic regions.

Catania, A., Ardissone, A., Verrigni, D., Legati, A., Reyes, A., Lamantea, E., et al. (2018). Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis. JOURNAL OF HUMAN GENETICS, 63(5), 563-568 [10.1038/s10038-018-0423-1].

Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis

CATANIA, ALESSIA;Ardissone, Anna;Ghezzi, Daniele
2018

Abstract

Biallelic mutations in NDUFAF6 have been identified as responsible for cases of autosomal recessive Leigh syndrome associated with mitochondrial complex I deficiency. Here we report two siblings and two unrelated subjects with Leigh syndrome, in which we found the same compound heterozygous missense (c.532G>C:p.A178P) and deep intronic (c.420+784C>T) variants in NDUFAF6. We demonstrated that the identified intronic variant creates an alternative splice site, leading to the production of an aberrant transcript. A detailed analysis of whole-exome sequencing data together with the functional validation based on mRNA analysis may reveal pathogenic variants even in non-exonic regions.
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Articolo in rivista - Articolo scientifico
Scientifica
Genetics; Genetics (clinical)
English
563
568
6
Catania, A., Ardissone, A., Verrigni, D., Legati, A., Reyes, A., Lamantea, E., et al. (2018). Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis. JOURNAL OF HUMAN GENETICS, 63(5), 563-568 [10.1038/s10038-018-0423-1].
Catania, A; Ardissone, A; Verrigni, D; Legati, A; Reyes, A; Lamantea, E; Diodato, D; Tonduti, D; Imperatore, V; Pinto, A; Moroni, I; Bertini, E; Robinson, A; Carrozzo, R; Zeviani, M; Ghezzi, D
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/205491
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