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Science 29 November 2002:
Vol. 298. no. 5599, pp. 1779 - 1781
DOI: 10.1126/science.1076521
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Reports

Truncating Neurotrypsin Mutation in Autosomal Recessive Nonsyndromic Mental Retardation

Florence Molinari,1 Marlène Rio,1 Virginia Meskenaite,2 Férechté Encha-Razavi,1 Joelle Augé,1 Delphine Bacq,3 Sylvain Briault,4 Michel Vekemans,1 Arnold Munnich,1 Tania Attié-Bitach,1 Peter Sonderegger,2 Laurence Colleaux1*

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.

1 Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, et Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
2 Institute of Biochemistry, University of Zurich, Switzerland.
3 Centre National de Génotypage, Evry, France.
4 Service de Génétique, CHU de Tours, Hôpital Bretonneau, Tours, France.
*   To whom correspondence should be addressed. E- mail: colleaux{at}necker.fr

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