Hemizygous deletions on chromosome 1p21.3 involving the DPYD gene in individuals with autism spectrum disorder
Hemizygous deletions on chromosome 1p21.3 involving the DPYD gene in individuals with autism spectrum disorder
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DOI：
10.1111/j.1399-0004.2010.01578.x
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发表时间：
2011-11-01
影响因子：
3.5
通讯作者：
Scherer, S. W.
中科院分区：
文献类型：
--
作者：
Carter, M. T.;Nikkel, S. M.;Scherer, S. W.
我们描述了来自三个不相关的家庭与半合子缺失涉及DPYD基因在染色体1p21.3的四个人的鉴定和临床表现。DPYD编码二氢嘧啶脱氢酶，它是嘧啶碱基分解代谢中的起始酶和限速酶。所有四个人都符合自闭症谱系障碍的诊断标准，伴有严重的语言延迟。患者1的删除最初于2008年报告，并提供了更详细的临床信息。随后，这名男性个体被发现在X连锁PTCHD 1自闭症易感基因中存在错义突变，这也可能导致表型。患者2和3是具有包括DPYD基因的新缺失的兄弟姐妹。在他们的母亲中，从染色体1p21.3删除的基因组区域被插入到染色体10中。第四个先证者有一个新的10-kb的DPYD基因外显子6基因内缺失检测到的更高分辨率的微阵列。我们的研究表明，涉及DPYD基因座的半合子缺失存在可变的表型，其中可能包括言语延迟和自闭症特征，并且还可能受到其他基因中其他突变的影响，这些问题需要在遗传咨询中考虑。
We describe the identification and clinical presentation of four individuals from three unrelated families with hemizygous deletions involving the DPYD gene at chromosome 1p21.3. DPYD encodes dihydropyrimidine dehydrogenase, which is the initial and rate-limiting enzyme in the catabolism of pyrimidine bases. All four individuals described met diagnostic criteria for autism spectrum disorder with severe speech delay. Patient 1's deletion was originally reported in 2008, and more detailed clinical information is provided. Subsequently, this male individual was found to have a missense mutation in the X-linked PTCHD1 autism susceptibility gene, which may also contribute to the phenotype. Patients 2 and 3 are siblings with a novel deletion encompassing the DPYD gene. In their mother, the genomic region deleted from chromosome 1p21.3 was inserted into chromosome 10. A fourth proband had a novel 10-kb intragenic deletion of exon 6 of the DPYD gene detected on a higher resolution microarray. Our study suggests that hemizygous deletions involving the DPYD locus present with variable phenotypes which can include speech delay and autistic features, and may also be influenced by additional mutations in other genes, issues which need to be considered in genetic counseling.