Hamdan Fadi F, Gauthier Julie, Spiegelman Dan, Noreau Anne, Yang Yan, Pellerin Stéphanie, Dobrzeniecka Sylvia, Côté Mélanie, Perreau-Linck Elizabeth, Carmant Lionel, D'Anjou Guy, Fombonne Eric, Addington Anjene M, Rapoport Judith L, Delisi Lynn E, Krebs Marie-Odile, Mouaffak Faycal, Joober Ridha, Mottron Laurent, Drapeau Pierre, Marineau Claude, Lafrenière Ronald G, Lacaille Jean Claude, Rouleau Guy A, Michaud Jacques L
Centre Hospitalier Universitaire Sainte-Justine Research Center, Centre of Excellence in Neuromics, Université de Montréal, QC, Canada.
N Engl J Med. 2009 Feb 5;360(6):599-605. doi: 10.1056/NEJMoa0805392.
Although autosomal forms of nonsyndromic mental retardation account for the majority of cases of mental retardation, the genes that are involved remain largely unknown. We sequenced the autosomal gene SYNGAP1, which encodes a ras GTPase-activating protein that is critical for cognition and synapse function, in 94 patients with nonsyndromic mental retardation. We identified de novo truncating mutations (K138X, R579X, and L813RfsX22) in three of these patients. In contrast, we observed no de novo or truncating mutations in SYNGAP1 in samples from 142 subjects with autism spectrum disorders, 143 subjects with schizophrenia, and 190 control subjects. These results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation.
尽管常染色体形式的非综合征性智力迟钝占智力迟钝病例的大多数，但其中涉及的基因在很大程度上仍不清楚。我们对94例非综合征性智力迟钝患者的常染色体基因SYNGAP1进行了测序，该基因编码一种对认知和突触功能至关重要的ras GTP酶激活蛋白。我们在其中三名患者中发现了新生的截短突变（K138X、R579X和L813RfsX22）。相比之下，在142例自闭症谱系障碍患者、143例精神分裂症患者和190例对照受试者的样本中，我们未观察到SYNGAP1有新生或截短突变。这些结果表明，SYNGAP1破坏是常染色体显性非综合征性智力迟钝的一个病因。
