NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)
Open accessAbstract
The hereditary spastic paraplegias (HSPs) are genetically heterogeneous disorders characterized by progressive lower-extremity weakness and spasticity. The molecular pathogenesis is poorly understood. We report discovery of a dominant negative mutation in the NIPA1 gene in a kindred with autosomal dominant HSP (ADHSP), linked to chromosome 15q11-q13 (SPG6 locus); and precisely the same mutation in an unrelated kindred with ADHSP that was too small for meaningful linkage analysis. NIPA1 is highly expressed in neuronal tissues and encodes a putative membrane transporter or receptor. Identification of the NIPA1 function and ligand will aid an understanding of axonal neurodegeneration in HSP and may have important therapeutic implications.
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NIPA1 is associated with autosomal dominant hereditary spastic paraplegia.
“NIPA1 or non-imprinted in Prader-Willi/Angelman syndrome 1 gene is the best studied gene within this region and associated with autosomal dominant hereditary spastic paraplegia [20,21].”
From The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review (2015) · cites this paper as [21]
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“NIPA1 or non-imprinted in Prader-Willi/Angelman syndrome 1 gene is the best studied gene within this region and associated with autosomal dominant hereditary spastic paraplegia [20,21].”
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- Authors
- Rainier, S., Chai, J.-H., Tokarz, D., Nicholls, R. D., & Fink, J. K.
- Affiliations
- University of Michigan (US)
- University of Pennsylvania (US)
- Corresponding author
- Fink, John K.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 73
- Issue
- 4
- Pages
- 967-971
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1180617
- OpenAlex
- W2066252692
- Cited by
- 207
- References
- 2
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 9 · 2013: 8 · 2012: 13
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (5r01ns036177-03, 5r01ns033645-06, 5r01ns038713-03)
- National Institute of Neurological Disorders and Stroke (R01 NS 38713, R01 NS33645, R01 NS 36177)
- National Institute of Environmental Health Sciences (ES10631, R01ES010631)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD31491, R01HD031491)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- NIPA1, dominant negative mutation, chromosome 15q11-q13, membrane transporters, spasticity, lower limb weakness
- MeSH terms
- Base Sequence, Female, Genes, Dominant, Humans, Male, Membrane Proteins, Models, Molecular, Mutation, Pedigree, Reference Values, Spastic Paraplegia, Hereditary, Protein Structure, Secondary
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