Aharoni, S; Barwick, KES; Straussberg, R; Harlalka, GV; Nevo, Y; Chioza, BA; McEntagart, MM; Mimouni-Bloch, A; Weedon, M; Crosby, AH
(2016)
Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel.
BMC Med Genetics, 17 (1).
p. 82.
ISSN 1471-2350
https://doi.org/10.1186/s12881-016-0343-x
SGUL Authors: McEntagart, Meriel
Abstract
BACKGROUND: CMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of "kinky" hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation. METHODS: An Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair. RESULTS: Here we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement. CONCLUSIONS: Our findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone.
Item Type: |
Article
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Additional Information: |
© The Author(s). 2016
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
Keywords: |
Charcot-Marie-Tooth disease type 2, GAN, Giant axonal neuropathy, Genetics & Heredity, 0604 Genetics, 1103 Clinical Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS) |
Journal or Publication Title: |
BMC Med Genetics |
ISSN: |
1471-2350 |
Language: |
eng |
Dates: |
Date | Event |
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16 November 2016 | Published | 7 November 2016 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
27852232 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/108445 |
Publisher's version: |
https://doi.org/10.1186/s12881-016-0343-x |
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