Clinical Exome Sequencing Identifies a Novel TUBB4A Mutation in a Child with Static Hypomyelinating Leukodystrophy

Purnell, Shawn M.; Bleyl, Steven B.; Bonkowsky, Joshua L.

doi:10.1016/j.pediatrneurol.2014.01.051

i

Clinical Exome Sequencing Identifies a Novel TUBB4A Mutation in a Child with Static Hypomyelinating Leukodystrophy

Supporting Files

Feb 10 2014
By Purnell, Shawn M. ; Bleyl, Steven B. ; Bonkowsky, Joshua L.

Details

Alternative Title:

Pediatr Neurol
Personal Author:

Purnell, Shawn M. ; Bleyl, Steven B. ; Bonkowsky, Joshua L.
Description:

Background

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.

Patient

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.

Results

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).

Conclusions

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.
Subjects:

Article Brain Child, Preschool DNA Mutational Analysis Exome Female Humans Hypomyelination Leukodystrophy Leukoencephalopathies Magnetic Resonance Imaging Mutation Phenotype TUBB4A Tubulin Whole Exome Sequencing
Source:

Pediatr Neurol. 2014; 50(6):608-611.
Pubmed ID:

24742798
Pubmed Central ID:

PMC4029864
Document Type:

Journal Article
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
Volume:

50
Issue:

6
Collection(s):

CDC Public Access
Main Document Checksum:

urn:sha256:ab55351363219fe022bc44141b9a82af6e295e5342b3d4cda0362a1907ff6659
Download URL:

https://stacks.cdc.gov/view/cdc/29964/cdc_29964_DS1.pdf
File Type:

[PDF - 219.11 KB ]

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