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.
Original language | English |
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Pages (from-to) | 563-568 |
Number of pages | 6 |
Journal | Journal of Human Genetics |
Volume | 63 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2018 |
Keywords
- Alleles
- Child
- Child, Preschool
- Female
- Fibroblasts/metabolism
- Gene Expression
- Haplotypes
- Heterozygote
- Humans
- Infant
- Introns
- Leigh Disease/diagnosis
- Lymphocytes/metabolism
- Magnetic Resonance Imaging/methods
- Male
- Mitochondrial Proteins
- Mutation, Missense
- Pedigree
- Phenotype
- RNA, Messenger/genetics
- Whole Exome Sequencing