Journal of Genomes and Exomes

Here we present a case in which exome sequencing rapidly produced a molecular diagnosis for a patient with hypomyelinating leukodystrophy, for whom years of costly conventional testing had not identified a molecular diagnosis. The patient had severe developmental delay, ataxia, nystagmus, external opthalmoplegia, hypometric saccades, and high myopia. Magnetic resonance imaging of the brain demonstrated severe failure of myelination of the corona radiate and centrum semi ovale. Through exome sequencing, two novel heterozygous missense variants were identified in the POLR3A gene (c.1160C . G; p.Ala387Gly and c.3781G . A; p.Glu1261 Lys). We propose the use of exome sequencing for the diagnosis of genetically heterogeneous conditions such as hypomyelinating leukodystrophy as a cost-effective primary diagnostic tool.