A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient
A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient
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DOI：
10.1016/j.neulet.2009.07.021
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发表时间：
2009-09-25
影响因子：
2.5
通讯作者：
Yoshikawa, Takeo
中科院分区：
文献类型：
--
作者：
Maekawa, Motoko;Iwayama, Yoshimi;Yoshikawa, Takeo
PAX6是一种在发育早期表达的转录因子，主要在眼睛、大脑和胰腺中表达。PAX6的突变导致包括无虹膜在内的眼部异常，并且还已知一些PAX6突变导致具有不完全自闭症的自闭症。我们对285名日本自闭症患者的PAX6的所有外显子和侧翼内含子进行了重新测序，新的突变可能是自闭症的基础。15个不同的多态性被确定：13个是新的，2个是以前报道过的（rs667773和rs3026393）。在这些新的突变中，有一个错义突变是在患者中发现的：136C > G（Leu46Val）（单核苷酸多态性ID“ss130452457”暂时指定）。Leu46从苍蝇到人类都是非常保守的，我们在2120名非自闭症受试者中没有检测到Val46。携带该杂合子突变的自闭症患者表现为视力下降、畏光和眼睑下垂，但没有其他眼部异常，如无虹膜。我们的研究结果表明，有必要进一步研究PAX6与自闭症之间的因果关系。(c)2009爱思唯尔爱尔兰有限公司保留所有权利。
The paired box 6 (PAX6) is a transcription factor expressed early in development, predominantly in the eye, brain and pancreas. Mutations in PAX6 are responsible for eye abnormalities including aniridia, and it is also known that some PAX6 mutations result in autism with incomplete penetrance. We resequenced all the exons and flanking introns of PAX6 in 285 autistic patients in the Japanese, with the possibility that novel mutations may underlie autism. Fifteen different polymorphisms were identified: 13 are novel, and 2 were previously reported (rs667773 and rs3026393). Among the novel ones, there is one missense mutation that was found in a patient: 136C > G (Leu46Val) (single nucleotide polymorphism ID "ss130452457" is temporarily assigned). Leu46 is extremely conserved from fly to human, and we did not detect Val46 in 2120 nonautistic subjects. The autistic patient carrying this heterozygous mutation showed reduced vision, photophobia and eyelid ptosis, but no other ocular abnormality such as aniridia. Our findings suggest the necessity of further studies on the causal relationship between PAX6 and autism. (c) 2009 Elsevier Ireland Ltd. All rights reserved.