Abstract
Background
Today, it is known that about 80 genes are involved in the etiology of hereditary
spastic paraplegia. However, there are many cases whose etiology could not be determined
by extensive genetic tests such as whole-exome sequencing, clinical exome.
Methods
Candidate genes were determined, since no clinically illuminating variant was detected
in the whole-exome sequencing analysis of three patients, two of whom were siblings,
with a complex hereditary spastic paraplegia phenotype.
Results
The p.Leu1202Pro variant in the SYNRG gene in the 1st and 2nd cases, and the p.Gly533* variant in the 3rd case were homozygous.
Discussion
We suggest that the SYNRG gene interacting with AP-1 (adaptor-related protein) from the AP complex family may
cause the complex hereditary spastic paraplegia phenotype with extensive clinical
spectrum. It may be important to evaluate SYNRG gene variants in patients with hereditary spastic paraplegia whose etiology has not
been clarified.
Keywords
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References
- Classification of the hereditary ataxias and paraplegias.Lancet. 1983; 321: 1151-1155
- A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum.J Neurol Sci. 2011; 305: 67-70
- Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: a population-based study.Brain. 2009; 132: 1577-1588
- Hereditary spastic paraplegia: from genes, cells and networks to novel pathways for drug discovery.Brain Sci. 2021; 11: 403
- Gamma-synergin: an EH domain-containing protein that interacts with gamma-adaptin.J Cell Biol. 1999; 146: 993-1004
- The Human Phenotype Ontology in 2021.Nucleic Acids Res. 2021; 49: D1207-D1217
- Neuronal functions of adaptor complexes involved in protein sorting.Curr Opin Neurobiol. 2018; 51: 103-110
- Outerwear through the ages: evolutionary cell biology of vesicle coats.Curr Opin Cell Biol. 2017; 47: 108-116
- Coatopathies: genetic disorders of protein coats.Annu Rev Cell Dev Biol. 2019; 35: 131-168
- Distinct and overlapping roles for AP-1 and GGAs revealed by the “knocksideways” system.Curr Biol. 2012; 22: 1711-1716
- Retrograde transport from endosomes to the trans-Golgi network.Nat Rev Mol Cell Biol. 2006; 7: 568-579
- Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features.Am J Med Genet A. 2014; 164: 1677-1685
- Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy.Am J Hum Genet. 2009; 85: 40-52
- Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48.Brain. 2014; 137: 1907-1920
- Familial spastic paraplegia with mental impairment and thin corpus callosum.J Neurol Sci. 1995; 131: 35-42
Article info
Publication history
Published online: January 25, 2022
Accepted:
January 5,
2022
Received in revised form:
January 5,
2022
Received:
December 1,
2021
Identification
Copyright
© 2022 The Japanese Society of Child Neurology Published by Elsevier B.V. All rights reserved.
