Brain involvement in Charcot-Marie-Tooth disease due to ganglioside-induced differentiation associated-protein 1 mutation.

Abstract

Charcot-Marie-Tooth (CMT) due to ganglioside-induced differentiation associated-protein 1 (GDAP1) gene mutation can be inherited as an autosomal recessive (severe phenotype) or dominant (milder phenotype) disorder. GDAP1 protein, located in the outer mitochondrial membrane, is involved in the mitochondrial fission. Brain imaging abnormalities have not been reported in this condition. We described an 8-year-old boy who had an early onset autosomal recessive neuropathy. Whole exome sequencing revealed compound heterozygous mutations in the GDAP1 gene: c.313_313delA, p.Arg105Glufs*3 - a novel mutation (maternally inherited) and c.358C>T, pR120W - a known pathogenic mutation (paternally inherited). He had abnormal brain MRI findings since infancy localized to the middle cerebellar peduncles and cerebellar white matter with sparing of the supratentorial brain. We speculate that GDAP1 protein due to its widespread distribution and mitochondrial location is responsible for these imaging abnormalities. This report expands the spectrum of brain imaging abnormalities seen in different types of CMT.

• Authors: Fouad Al-Ghamdi, Irina Anselm, Edward Yang, Partha S Ghosh
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 27 Issue 9 Pg. 848-851 (Sep 2017) ISSN: 1873-2364 [Electronic] England
• PMID: 28673555 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• GDAP protein
• Nerve Tissue Proteins

Topics

• Brain (diagnostic imaging, pathology)
• Charcot-Marie-Tooth Disease (diagnostic imaging, genetics, pathology)
• Child
• Female
• Humans
• Magnetic Resonance Imaging
• Mutation (genetics)
• Nerve Tissue Proteins (genetics)
• Pregnancy