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

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

Published Date:

Feb 10 2014

Publisher's site:

http://dx.doi.org/10.1016/j.pediatrneurol.2014.01.051 New Site Icon

Source:

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

[PDF-219.11 KB]

Details:

Personal Authors:

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

Keywords:

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Pubmed ID:

24742798

Pubmed Central ID:

PMC4029864

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.

Document Type:

Journal Article

Collection(s):

CDC Public Access

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

Main Document Checksum:

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Supporting Files:

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