Inborn errors of metabolismGene: ISCU
This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
Created: 15 Aug 2019, 12:15 p.m. | Last Modified: 15 Aug 2019, 12:15 p.m.
Panel Version: 1.156
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, 11:17 a.m. | Last Modified: 12 Aug 2019, 11:17 a.m.
Panel Version: 1.79
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
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
Myopathy with lactic acidosis, hereditary, MIM#255125
Variants in this GENE are reported as part of current diagnostic practice
Tag non-coding-known-pathogenic tag was added to gene: ISCU.
Publications for gene: ISCU were set to 18304497; 29079705; 18296749; 19567699; 20206689
Mode of inheritance for gene: ISCU was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source Expert Review Green was added to ISCU. Mode of inheritance for gene ISCU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes Myopathy with lactic acidosis, hereditary, 255125; Disorders of iron homeostasis for gene: ISCU Publications for gene ISCU were changed from 27604308 to 18304497; 29079705; 18296749; 19567699; 20206689 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Source NHS GMS was added to ISCU. Source London North GLH was added to ISCU.
Sarah Leigh: Associated with relevant pheno
Added phenotypes Myopathy with lactic acidosis, hereditary, 255125; Disorders of iron homeostasis for gene: ISCU
gene: ISCU was added gene: ISCU was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: ISCU was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ISCU were set to 27604308 Phenotypes for gene: ISCU were set to Rhabdomyolysis and metabolic muscle disorders; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))