Truncating Neurotrypsin Mutation in Autosomal Recessive Nonsyndromic Mental Retardation
Abstract
A 4–base pair deletion in the neuronal serine protease neurotrypsin gene was associated with autosomal recessive nonsyndromic mental retardation (MR). In situ hybridization experiments on human fetal brains showed that neurotrypsin was highly expressed in brain structures involved in learning and memory. Immuno-electron microscopy on adult human brain sections revealed that neurotrypsin is located in presynaptic nerve endings, particularly over the presynaptic membrane lining the synaptic cleft. These findings suggest that neurotrypsin-mediated proteolysis is required for normal synaptic function and suggest potential insights into the pathophysiological bases of mental retardation.
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Several highly selective markers for RCs have been implicated as risk factors for neuropsychiatric disease, including netrin G1 (NTNG1) for Rett syndrome and neurotrypsin (PRSS12) for mental retardation.
“For example, several highly selective markers for RCs have been implicated as risk factors for neuropsychiatric disease, including netrin G1 (NTNG1) for Rett syndrome47 and neurotrypsin (PRSS12) for mental retardation48.”
From Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (2018) · cites this paper as [48]
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- Authors
- Molinari, F., Rio, M., Meskenaite, V., Encha-Razavi, F., Augé, J., Bacq, D., Briault, S., Vekemans, M., Munnich, A., Attié-Bitach, T., Sonderegger, P., & Colleaux, L.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, et Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
- Institute of Biochemistry, University of Zurich, Switzerland.
- Centre National de Génotypage, Evry, France.
- Centre Hospitalier Universitaire de Tours (FR)
- University of Zurich (CH)
- Corresponding author
- Colleaux, Laurence
- Venue
- Science
- Published
- 2002-11-29
- Volume
- 298
- Issue
- 5599
- Pages
- 1779-1781
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2131114792
- Cited by
- 184
- References
- 27
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 8 · 2014: 12 · 2013: 13 · 2012: 9
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- gene truncation, synaptic cleft, learning and memory, neurodegeneration
- MeSH terms
- Adolescent, Adult, Brain, Female, Fetus, Genes, Recessive, Humans, Immunohistochemistry, Male, Intellectual Disability, Pedigree, Serine Endopeptidases, Spinal Cord, Synapses, Synaptic Membranes, Gene Expression, Microscopy, Immunoelectron, Sequence Deletion, Microsatellite Repeats
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