CAGSSS stands for a syndrome presenting with cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss and skeletal dysplasia. It is a very rare disorder for which so far only a single extended patient family of Franco-Canadian descent had been reported. Its genetic cause is a mutation in IARS2, a gene encoding the mitochondrial isoleucine tRNA synthetase.

Together with collaboration partners in Denmark, South Korea and Japan, researchers of the Institute of Human Genetics Göttingen have now identified a novel homozygous missense mutation in IARS2 by whole-exome sequencing in a Danish patient. Interestingly, the clinical picture of the girl was first dominated by bilateral hip dislocation, short stature, and hypotonia combined with skeletal anomalies that initially suggested spondyloepimetaphyseal dysplasia (SEMD). Several other CAGSSS-typical features like cataracts, peripheral neuropathy and hearing loss became only manifest over time.

The study describes the second family worldwide with IARS2 mutation and confirms that variations in a mitochondrial-related gene may lead to skeletal dysplasia. The results of the study have recently been published in the American Journal of Medical Genetics.

Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2
Moosa S, Haagerup A, Gregersen PA, Petersen KK, Altmüller J, Thiele H, Nürnberg P, Cho TJ, Kim OH, Nishimura G, Wollnik B, Vogel I
Am J Med Genet Part A 2017;173A:1102–1108. doi: 10.1002/ajmg.a.38116.