Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2

Tools

Item Type:	Article
Title:	Confirmation of CAGSSS syndrome as a distinct entity in a Danish patient with a novel homozygous mutation in IARS2
Creators Name:	Moosa, S., Haagerup, A., Gregersen, P.A., Petersen, K.K., Altmüller, J., Thiele, H., Nürnberg, P., Cho, T.J., Kim, O.H., Nishimura, G., Wollnik, B. and Vogel, I.
Abstract:	Since the original description of the IARS2-related cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, skeletal dysplasia syndrome (CAGSSS; OMIM 616007) in an extended consanguineous family of French-Canadian descent, no further patients have been reported. IARS2 (OMIM 612801) encodes the mitochondrial isoleucine-tRNA synthetase which belongs to the class-I aminoacyl-tRNA synthetase family, and has been implicated in CAGSSS and a form of Leigh syndrome. Here, we report on a female Danish patient with a novel homozygous IARS2 mutation, p.Gly874Arg, who presented at birth with bilateral hip dislocation and short stature. At 3 months, additional dysmorphic features were noted and at 18 months her radiographic skeletal abnormalities were suggestive of an underlying spondyloepimetaphyseal dysplasia (SEMD). Retrospective analysis of the neonatal radiographs confirmed that the skeletal changes were present at birth. It was only with time that several of the other manifestations of the CAGSSS emerged, namely, cataracts, peripheral neuropathy, and hearing loss. Growth hormone deficiency has not (yet) manifested. We present her clinical features and particularly highlight her skeletal findings, which confirm the presence of a primary SEMD skeletal dysplasia in a growing list of mitochondrial-related disorders including CAGSSS, CODAS, EVEN-PLUS, and X-linked SEMD-MR syndromes.
Keywords:	CAGSSS, IARS2, Mitochondrial Disorder, SEMD, Skeletal Dysplasia
Source:	American Journal of Medical Genetics Part A
ISSN:	1552-4825
Publisher:	Wiley
Volume:	173
Number:	4
Page Range:	1102-1108
Date:	April 2017
Official Publication:	https://doi.org/10.1002/ajmg.a.38116
PubMed:	View item in PubMed

Repository Staff Only: item control page