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.

Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis / A. Catania, A. Ardissone, D. Verrigni, A. Legati, A. Reyes, E. Lamantea, D. Diodato, D. Tonduti, V. Imperatore, A.M. Pinto, I. Moroni, E. Bertini, A. Robinson, R. Carrozzo, M. Zeviani, D. Ghezzi. - In: JOURNAL OF HUMAN GENETICS. - ISSN 1434-5161. - (2018 Mar 12). [Epub ahead of print] [10.1038/s10038-018-0423-1]

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

D. Tonduti;D. Ghezzi
Ultimo
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.
Settore MED/03 - Genetica Medica
Settore MED/26 - Neurologia
Settore BIO/13 - Biologia Applicata
12-mar-2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/567363
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