Team Manipal discovers a new mitochondrial genetic disease – QS WOW News (press release) (registration)

India The department of medical genetics at Kasturba Medical College, Manipal (a constituent college of Manipal University), led by Dr Girish Katta, has discovered a new genetic disease called multiple mitochondrial dysfunction syndrome. Defects in ISCA1 gene are the likely cause of the disease in four children from two families in the region.

The team comprising clinical geneticist Dr Anju Shukla studied two families with a severe neurological disease in infancy. All four affected children died early in childhood. DNA from the first family was analysed by exome sequencing. The bioinformatics analysis then identified a similarly affected family from the in-house database of exomes. All the four children showed a severe white matter disease of brain.

The iron-sulfur (Fe-S) cluster (ISC) biogenesis pathway is indispensable for many fundamental biological processes, and pathogenic variations in genes encoding several components of the Fe-S biogenesis machinery, such as NFU1, BOLA3, IBA57 and ISCA2, are already implicated in causing four types of multiple mitochondrial dysfunctions syndromes (MMDS). The two unrelated families, with two affected children each with early onset neurological deterioration, seizures, extensive white matter abnormalities, cortical migrational abnormalities, lactic acidosis and early demise were investigated. Exome sequencing identified a homozygous c.259G>A [p.(Glu87Lys)] variant in ISCA1 gene. This was due to a founder effect. The phenotype observed in all affected subjects with the ISCA1 pathogenic variant is similar to that previously described in all four types of multiple mitochondrial dysfunctions syndrome (MMDS).

The findings suggest association of a pathogenic variant in ISCA1 with another new type MMDS, added Dr Vinod Bhat, vice chancellor of Manipal University. The research work was funded by National Institutes of Health (NIH), USA.

The work is now published online in the highly reputed Journal of Human Genetics, published by Nature Publishing Group. A new bone disease short rib thoracic dysplasia type 16, which was identified by the same team, has already been catalogued in Online Mendelian Inheritance in Man (OMIM) following discovery of similar disease from United States of America.

More:
Team Manipal discovers a new mitochondrial genetic disease - QS WOW News (press release) (registration)