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A NOVEL WHITE MATTER DISORDER WITH CEREBRAL HYPOMYELINATION AND CONGENITAL CATARACT
Objectives: To describe clinical, neuroradiological and molecular findings of a novel white matter disorder with cerebral hypomyelination and congenital cataract.
Methods: The systematic analysis of cases with unclassified leukoencephalopathies allowed us to identify 10 patients showing congenital cataract, slowly progressive neurological impairment, and diffuse white matter abnormalities on MRI.
Results: All patients presented with congenital cataract. Psychomotor developmental delay was evident after the first year of life. All cases achieved the ability of walking with support only, and they lost this ability with time. Neurological examination showed pyramidal and cerebellar signs. Mental retardation ranged from mild to moderate. Peripheral neuropathy was demonstrated by neurophysiological studies in 9/10. MRI showed global involvement of the supratentorial white matter, with preservation of both cortical and deep gray matter structures. There was no abnormal contrast enhancement. Linkage studies led to the identification of a 3.2 Mb homozygous segment in all affected patients. The typing of 10–15 kb spaced SNPs and microsatellite markers led to the definition of the critical region harbouring 14 fulllenght transcripts. Three different mutations were identified in a gene of unknown function. Additional studies are being carried on to clarify the function of this gene and the pathogenesis of the disorder.
Conclusion: The ten cases share a common neurological, neuroradiological and molecular phenotype. We therefore propose that this syndrome represents a novel autosomal recessive white matter disorder.