title: 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.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, et Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Molinari
authors.forename: Marlene
authors.initials: M
authors.lastname: Rio
authors.forename: Virginia
authors.initials: V
authors.lastname: Meskenaite
authors.forename: Férechté
authors.initials: F
authors.lastname: Encha-Razavi
authors.forename: Joelle
authors.initials: J
authors.lastname: Augé
authors.forename: Delphine
authors.initials: D
authors.lastname: Bacq
authors.forename: Sylvain
authors.initials: S
authors.lastname: Briault
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
authors.forename: Peter
authors.initials: P
authors.lastname: Sonderegger
authors.forename: Laurence
authors.initials: L
authors.lastname: Colleaux
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D005808:Genes, Recessive; D006801:Humans; D007150:Immunohistochemistry; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D016253:Microscopy, Immunoelectron; D010375:Pedigree; D017384:Sequence Deletion; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: D012697:Serine Endopeptidases; C108493:neurotrypsin