{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:42:45Z","timestamp":1791160965199,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,9,3]]},"abstract":"<jats:p>\n                    In the last few years, several genes involved in X-specific mental retardation (MR) have been identified by using genetic analysis. Although it is likely that additional genes responsible for idiopathic MR are also localized on the autosomes, cloning and characterization of such genes have been elusive so far. Here, we report the isolation of a previously uncharacterized gene,\n                    <jats:italic>MEGAP<\/jats:italic>\n                    , which is disrupted and functionally inactivated by a translocation breakpoint in a patient who shares some characteristic clinical features, such as hypotonia and severe MR, with the 3p\n                    <jats:sup>\u2212<\/jats:sup>\n                    syndrome. By fluorescence\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization and loss of heterozygosity analysis, we demonstrated that this gene resides on chromosome 3p25 and is deleted in 3p\n                    <jats:sup>\u2212<\/jats:sup>\n                    patients that present MR.\n                    <jats:italic>MEGAP<\/jats:italic>\n                    \/\n                    <jats:italic>srGAP3<\/jats:italic>\n                    mRNA is predominantly and highly expressed in fetal and adult brain, specifically in the neurons of the hippocampus and cortex, structures known to play a pivotal role in higher cognitive function, learning, and memory. We describe several\n                    <jats:italic>MEGAP<\/jats:italic>\n                    \/\n                    <jats:italic>srGAP3<\/jats:italic>\n                    transcript isoforms and show that MEGAP\/srGAP3\n                    <jats:italic>a<\/jats:italic>\n                    and -\n                    <jats:italic>b<\/jats:italic>\n                    represent functional GTPase-activating proteins (GAP) by an\n                    <jats:italic>in vitro<\/jats:italic>\n                    GAP assay. MEGAP\/srGAP3 has recently been shown to be part of the Slit-Robo pathway regulating neuronal migration and axonal branching, highlighting the important role of MEGAP\/srGAP3 in mental development. We propose that haploinsufficiency of\n                    <jats:italic>MEGAP<\/jats:italic>\n                    \/\n                    <jats:italic>srGAP3<\/jats:italic>\n                    leads to the abnormal development of neuronal structures that are important for normal cognitive function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.162241099","type":"journal-article","created":{"date-parts":[[2002,9,3]],"date-time":"2002-09-03T15:58:55Z","timestamp":1031068735000},"page":"11754-11759","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":199,"title":["The novel Rho-GTPase activating gene\n                    <i>MEGAP<\/i>\n                    \/\n                    <i>srGAP3<\/i>\n                    has a putative role in severe mental retardation"],"prefix":"10.1073","volume":"99","author":[{"given":"Volker","family":"Endris","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; Zentralinstitut f\u00fcr Seelische Gesundheit, J5, 68159 Mannheim, Germany; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; and Klinik f\u00fcr Kinderneurologie und Sozialpaediatrie, Kinderzentrum Maulbronn, 75433 Maulbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Wogatzky","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; Zentralinstitut f\u00fcr Seelische Gesundheit, J5, 68159 Mannheim, Germany; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; and Klinik f\u00fcr Kinderneurologie und Sozialpaediatrie, Kinderzentrum Maulbronn, 75433 Maulbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Leimer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; Zentralinstitut f\u00fcr Seelische Gesundheit, J5, 68159 Mannheim, Germany; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; and Klinik f\u00fcr Kinderneurologie und Sozialpaediatrie, Kinderzentrum Maulbronn, 75433 Maulbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; Zentralinstitut f\u00fcr Seelische Gesundheit, J5, 68159 Mannheim, Germany; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; and Klinik f\u00fcr Kinderneurologie und Sozialpaediatrie, Kinderzentrum Maulbronn, 75433 Maulbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Zatyka","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; 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Zentralinstitut f\u00fcr Seelische Gesundheit, J5, 68159 Mannheim, Germany; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; and Klinik f\u00fcr Kinderneurologie und Sozialpaediatrie, Kinderzentrum Maulbronn, 75433 Maulbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamali","family":"Tariverdian","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; Zentralinstitut f\u00fcr Seelische Gesundheit, J5, 68159 Mannheim, Germany; Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham Medical School, Edgbaston, Birmingham B15 2TT, United Kingdom; and Klinik f\u00fcr Kinderneurologie und Sozialpaediatrie, Kinderzentrum Maulbronn, 75433 Maulbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kirsch","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Universit\u00e4t Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany; 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