Clinical Exome Sequencing Identifies a Novel TUBB4A Mutation in a Child with Static Hypomyelinating Leukodystrophy
Published Date:Feb 10 2014
Source:Pediatr Neurol. 2014; 50(6):608-611.
Pubmed Central ID:PMC4029864
Funding:DP2 MH100008/MH/NIMH NIH HHS/United States
DP2 MH10008/DP/NCCDPHP CDC HHS/United States
T35 HL07744/HL/NHLBI NIH HHS/United States
Leukodystrophies are a large group of inherited diseases of CNS myelin. There are few treatments, and a majority of patients do not receive a final genetic diagnosis.
We report a novel presentation of a female child with hypotonia, global developmental delay, and rotatory nystagmus. Brain MRI demonstrated profound hypomyelination; and minimal or no atrophy in the brain stem or cerebellum.
Extensive testing failed to yield a diagnosis until clinical whole exome sequencing revealed a novel pathogenic mutation in the β-tubulin gene TUBB4A. TUBB4A is a cause of hereditary dystonia type 4 (DYT4) and has recently been reported to cause hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC).
This report expands the phenotypic spectrum of TUBB4A-associated neurological diseases to include static hypomyelinating leukodystrophy and supports the clinical relevance of next generation sequencing diagnosis approaches.
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