Truncating neurotrypsin mutation in autosomal recessive nonsyndromic mental retardation.
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.
Molinari
Florence
F
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, et Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
Rio
Marlene
M
Meskenaite
Virginia
V
Encha-Razavi
Férechté
F
Augé
Joelle
J
Bacq
Delphine
D
Briault
Sylvain
S
Vekemans
Michel
M
Munnich
Arnold
A
Attié-Bitach
Tania
T
Sonderegger
Peter
P
Colleaux
Laurence
L
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
D012697:Serine Endopeptidases; C108493:neurotrypsin