Diffuse hypomyelination is not obligate for POLR3-related disorders

WOS: 000375050100016PubMed ID: 27029625Objective:To report atypical MRI patterns associated with POLR3A and POLR3B mutations.Methods:This was a multicenter retrospective study to collect neuroradiologic, clinical, and molecular data of patients with mutations in POLR3A and POLR3B without the classic MRI phenotype, i.e., diffuse hypomyelination associated with relative T2 hypointensity of the ventrolateral thalamus, globus pallidus, optic radiation, corticospinal tract at the level of the internal capsule, and dentate nucleus, cerebellar atrophy, and thinning of the corpus callosum.Results:Eight patients were identified: 6 carried mutations in POLR3A and 2 in POLR3B. We identified 2 novel MRI patterns: 4 participants presented a selective involvement of the corticospinal tracts, specifically at the level of the posterior limbs of the internal capsules; 4 patients presented moderate to severe cerebellar atrophy. Incomplete hypomyelination was observed in 5 participants.Conclusion:Diffuse hypomyelination is not an obligatory feature of POLR3-related disorders. Two distinct patterns, selective involvement of the corticospinal tracts and cerebellar atrophy, are added to the MRI presentation of POLR3-related disorders.Fonds de recherche du Quebec-Sante (FRQS); Fondation Monaco; Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia; Fonds de Recherche du Quebec en Sante (FRQS); ZonMw (TOP grant) [91211005]; Canadian Institute for Health ResearchCanadian Institutes of Health Research (CIHR) [MOP-G-287547]; Reseau de Medecine Genetique Appliquee du FRQS; BMBF through the Juniorverbund in der Systemmedizin "mitOmics"Federal Ministry of Education & Research (BMBF) [FKZ 01ZX1405C]R.L.P. has received a Doctoral Award from the Fonds de recherche du Quebec-Sante (FRQS) and has been supported by the Fondation Monaco. F.K.C. is a recipient of the Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia. G.B. has received a Research Scholar Junior 1 award from the Fonds de Recherche du Quebec en Sante (FRQS). N.I.W. and M.S.v.d.K. are supported by ZonMw (TOP grant 91211005). This work was supported by Canadian Institute for Health Research grant MOP-G-287547 and the Reseau de Medecine Genetique Appliquee du FRQS to G.B. T.H. was supported by the BMBF through the Juniorverbund in der Systemmedizin "mitOmics" (FKZ 01ZX1405C)