Compound heterozygous missense and deep intronic variants in NDUFAF6 unraveled by exome sequencing and mRNA analysis.
J Hum Genet
; 63(5): 563-568, 2018 May.
Article
in En
| MEDLINE
| ID: mdl-29531337
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>Cp.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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Introns
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Leigh Disease
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Mutation, Missense
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Exome Sequencing
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Heterozygote
Type of study:
Prognostic_studies
Limits:
Child
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Child, preschool
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Female
/
Humans
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Infant
/
Male
Language:
En
Journal:
J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2018
Document type:
Article
Affiliation country:
Italia