Mitochondrial disorders

Gene: ISCU

Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant in ISCU associated with mitochondrial myopathy, which justifies the mode of inheritance recorded here.

Created: 12 Aug 2019, 11:15 a.m. | Last Modified: 12 Aug 2019, 11:15 a.m.

Panel Version: 1.477

Comment on list classification: Sufficient published reported biallelic cases, with supportive functional studies. The most frequent reported variant c.343+382G>C g.108567650G>C is deep in intron five of the gene and strengthens a weak splicing acceptor site, with consequent retention of a 100-bp intronic sequence upstream of the known terminal exon, introduction of a stop codon and decreased levels of ISCU mRNA and protein (PMID 18304497). This may be missed by standard sequencing.

Created: 16 Apr 2019, 2:32 p.m. | Last Modified: 6 Aug 2019, 10:57 a.m.

Panel Version: 1.469

Publications

• 18304497

Green List (high evidence)

Multiple individuals mostly from Swedish ancestry reported in the literature; there is a common founder variant, which has been observed in combination with a number of other variants. Please also note report of a patient with a de novo single variant in this gene, and disease, backed up with functional data.

Created: 30 Aug 2018, 5:52 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathy with lactic acidosis, hereditary, MIM#255125

Publications

• 18296749
• 29079705
• 19567699
• 20206689

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)