An intermediate phenotype in IDH related enchondromatosis spectrum

Abstract

Mosaic variants of IDH1 (isocitrate dehydrogenase-1) R132 and IDH2 (isocitrate dehydrogenase-2) R172 loci were detected in most of the bone cysts of Ollier and Maffucci series and in the blood and tissue samples of metaphyseal enchondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA) patients. We aimed to report an intermediate phenotype comparing with the reported cases. The proband was a 9-year-old boy with widespread metaphyseal enchondromatosis involving metaphyses of long tubular bones, iliac bones and tubular bones of both hands and feet and sparing spine and flat and short bones. He underwent quad whole exome sequencing (index-both parents-healthy sibling). Sanger sequencing was performed for confirmation and segregation purposes. Heterozygous IDH1 R132H (c.395G > A) variant was detected in his blood via whole exome sequencing and Sanger analysis in mosaic state, 22% of the reads and Sanger signal. He had no D-2-hydroxyglutaric aciduria in urinary organic acid analysis. Our case is unique with the presence of IDH1 R132H variant in blood with metaphyseal enchondromatosis without D-2-hydroxyglutaric aciduria. It was a transitional phenotype. With his phenotype, we expand the IDH1/IDH2 related enchondromatosis phenotypes.

Keywords: Enchondromatosis; IDH1; Metaphyseal enchondromatosis with D-2- hydroxyglutaric aciduria (MC-HGA); Skeletal dysplasia; Whole exome sequencing.