Cited by 184Genetics and Neurodevelopmental DisordersDown syndrome and intellectual disability researchProtease and Inhibitor Mechanisms

Truncating Neurotrypsin Mutation in Autosomal Recessive Nonsyndromic Mental Retardation

Molinari, Florence, Rio, Marlène, Meskenaite, Virginia, Encha-Razavi, Férechté, Augé, Joelle, Bacq, Delphine, Briault, Sylvain, Vekemans, Michel +4 more·2002·Science

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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Crossref · 10.1126/science.1076521

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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.”

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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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