Journal article

Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Yanick J Crow, Heather Marshall, Gillian Rice, Luis Seabra, Emma M Jenkinson, Kristin Baranano, Roberta Battini, Andrea Berger, Edward Blair, Thomas Blauwblomme, Francois Bolduc, Natalie Boddaert, Johannes Buckard, Heather Burnett, Sophie Calvert, Roseline Caumes, Andy Cheuk-Him Ng, Diana Chiang, David B Clifford, Duccio M Cordelli Show all



Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 5..

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Awarded by Great Ormond Street Hospital Charity

Awarded by National Research Agency (France)

Awarded by Estonian Research Council

Funding Acknowledgements

We sincerely thank all the patients, their families and collaborating physicians who provided help in compiling the information included in this manuscript. The study was supported by a grant to Y. J. C. and R. T. O'K. from the Great Ormond Street Hospital Charity (V4017). Y. J. C. also acknowledges a state subsidy managed by the National Research Agency (France) under the "Investments for the Future" program bearing the reference ANR-10-IAHU-01 and the MSDAvenir fund (DEVO-DECODE Project). The University of Cambridge has received salary support in respect of R.S. from the NHS in the East of England through the Clinical Academic Reserve. In this regard, the views expressed are those of the authors and not necessarily those of the NHS or Department of Health. K.O. is supported by an Estonian Research Council grant (PRG471).