Brief report: Aggression and stereotypic behavior in males with fragile X syndrome - Moderating secondary genes in a "Single Gene" disorder
Brief report: Aggression and stereotypic behavior in males with fragile X syndrome - Moderating secondary genes in a "Single Gene" disorder
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DOI：
10.1007/s10803-007-0365-5
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发表时间：
2008-01-01
影响因子：
3.9
通讯作者：
Hagerman, Randi J.
中科院分区：
文献类型：
--
作者：
Hessl, David;Tassone, Flora;Hagerman, Randi J.
虽然脆性X综合征（FXS）是一种具有良好描述表型的单基因疾病，但尚不清楚为什么有些个体会出现更严重的适应不良行为，如攻击或自闭症症状。在这里，我们研究了两个候选基因已知影响情绪和侵略，5-羟色胺转运体（5-HTTLPR）和单胺氧化酶A（MAOA-VNTR）多态性，在50名男性与FXS年龄8-24岁。参与者的母亲和父亲报告了攻击性/破坏性，自我伤害和刻板行为的频率和严重程度。多态性基因型与年龄、智商无关。结果显示5-HTTLPR基因型对攻击性/破坏性和刻板行为有显著影响;高转录长（L/L）基因型纯合的FXS男性具有最具攻击性和破坏性的行为，而短（S/S）基因型纯合的个体具有最少的攻击性。具有L/L基因型的人也具有最高水平的刻板行为。MAOA-VNTR对行为没有影响;然而，那些具有高活性，4重复基因型的人更有可能服用SSRI或SNRI药物。这一初步研究提示考虑可能改变神经发育障碍行为表型表达的次级基因，即使是那些具有单基因病因的神经发育障碍，如FXS。
Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA-VNTR) polymorphisms, in 50 males with FXS ages 8-24 years. Mothers and fathers of participants reported the frequency and severity of aggressive/destructive, self-injurious, and stereotypic behaviors. Polymorphism genotypes were unrelated to age and IQ. Results showed a significant effect of 5-HTTLPR genotype on aggressive/destructive and stereotypic behavior; males with FXS who were homozygous for the high-transcribing long (L/L) genotype had the most aggressive and destructive behavior, and individuals homozygous for the short (S/S) genotype had the least aggression. Those with the L/L genotype also had the highest levels of stereotypic behavior. There was no effect of MAOA-VNTR on behavior; however those with the high-activity, 4-repeat genotype were more likely to be taking SSRI or SNRI medication. This preliminary study prompts consideration of secondary genes that may modify behavioral phenotype expression in neurodevelopmental disorders, even those with a single gene etiology such as FXS.