Journal article
Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss
Neurology Genetics, Vol.1(2), e16
2015
Abstract
Objective: To determine the molecular basis of a severe neurologic disorder in a large consanguineous family with complete agenesis of the corpus callosum (ACC), pontocerebellar hypoplasia (PCH), and peripheral axonal neuropathy.
Methods: Assessment included clinical evaluation, neuroimaging, and nerve conduction studies (NCSs). Linkage analysis used genotypes from 7 family members, and the exome of 3 affected siblings was sequenced. Molecular analyses used Sanger sequencing to perform segregation studies and cohort analysis and Western blot of patient-derived cells.
Results: Affected family members presented with postnatal microcephaly and profound developmental delay, with early death in 3. Neuroimaging, including a fetal MRI at 30 weeks, showed complete ACC and PCH. Clinical evaluation showed areflexia, and NCSs revealed a severe axonal neuropathy in the 2 individuals available for electrophysiologic study. A novel homozygous stopgain mutation in adenosine monophosphate deaminase 2 (AMPD2) was identified within the linkage region on chromosome 1. Molecular analyses confirmed that the mutation segregated with disease and resulted in the loss of AMPD2. Subsequent screening of a cohort of 42 unrelated individuals with related imaging phenotypes did not reveal additional AMPD2 mutations.
Conclusions: We describe a family with a novel stopgain mutation in AMPD2. We expand the phenotype recently described as PCH type 9 to include progressive postnatal microcephaly, complete ACC, and peripheral axonal neuropathy. Screening of additional individuals with related imaging phenotypes failed to identify mutations in AMPD2, suggesting that AMPD2 mutations are not a common cause of combined callosal and pontocerebellar defects.
Details
- Title
- Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss
- Authors/Creators
- A.P.L. Marsh (Author/Creator)V. Lukic (Author/Creator)K. Pope (Author/Creator)C. Bromhead (Author/Creator)R. Tankard (Author/Creator)M.M. Ryan (Author/Creator)E.M. Yiu (Author/Creator)J.C.H. Sim (Author/Creator)M.B. Delatycki (Author/Creator)D.J. Amor (Author/Creator)G. McGillivray (Author/Creator)E.H. Sherr (Author/Creator)M. Bahlo (Author/Creator)R.J. Leventer (Author/Creator)P.J. Lockhart (Author/Creator)
- Publication Details
- Neurology Genetics, Vol.1(2), e16
- Publisher
- Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
- Identifiers
- 991005540596607891
- Copyright
- © 2015 American Academy of Neurology
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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