The changing face of Arabian dust storms
01 June 2023
Published online 16 August 2017
A new study opens up potential routes for the future treatment of Galloway–Mowat syndrome, an extremely rare but deadly genetic kidney and brain disease.
Fresh investigations of the protein complex, KEOPS, have implicated specific mutations in gene encoding in GAMOS, a severe genetic disorder that causes developmental and physical abnormalities1.
GAMOS manifests as combined nephrotic syndrome, a kidney disease which carries symptoms such as loss of protein in the urine, low blood albumin levels, swelling, and primary microcephaly, a neurodevelopmental condition that causes non-progressive mental retardation, and in which infants are born with small heads and brains.
“Our work is centered on an enigmatic protein complex that to date has only been subject of few scientific publications,” says Friedhelm Hildebrandt, professor of pediatrics at Harvard Medical School and senior author of the study. “However, it plays a role in the evolving field of disturbed tRNA modification as novel pathogenic mechanisms of human diseases.“
Patients with GAMOS frequently die early in childhood, says Hildebrandt. By understanding the effect of mutations in the genes encoding this protein complex, researchers are able to find links between this complex and the disease.
“Our genetics data highlight the importance of KEOPS complex function for mammalian organisms and suggest that certain organ system (postmitotic cells) are particularly sensitive to disturbed KEOPS complex function,” he says.
The study, carried out by 104 investigators from 19 different countries, identifies four new GAMOS causes that involve a single gene, delineating potential pathogenic mechanisms.
Identifying these causes of GAMOS is a breakthrough as “monogenic forms of nephrotic syndrome are typically resistant to drug treatment and invariably progress to end-stage renal failure requiring dialysis or renal transplantation for survival,” says Harvard Medical School’s Daniela Braun, first author on this study.