Macrocephaly as a clinical indicator of genetic subtypes in autism.
Macrocephaly as a clinical indicator of genetic subtypes in autism.
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DOI：
10.1002/aur.1266
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发表时间：
2013-02
期刊：
影响因子：
4.7
通讯作者：
Martinez-Agosto, Julian A.
中科院分区：
文献类型：
--
作者：
Klein, Steven;Sharifi-Hannauer, Pantea;Martinez-Agosto, Julian A.
之前已经描述过自闭症和大头之间的联系。从历史上看，这些病例的一部分与磷酸酶和张力蛋白同源基因(PTEN)的突变有关。然而，对于大多数病例，病因尚不清楚。我们研究了33名患有自闭症和大头型的患者。在这一组中，我们确认了PTEN突变与极端头部大小的关联，并在22%的病例中发现了突变，包括三个新的PTEN突变。此外，我们定义了三个新的表型亚型：(1)与躯体过度生长有关的病例(2)不成比例的大头畸形病例和(3)相对巨头畸形病例。这些亚组中的成员缺乏PTEN基因的变化，此外，我们还报告了这些患者中两个新的拷贝数变化。自闭症和巨头畸形之间的联系之前已经被描述过了。极大头畸形(>；3SD，99.7%的ILE)病例的子集与基因磷酸酶和紧张素同源基因(PTEN)的突变有关。然而，其余病例的表型和基因特征仍不清楚。我们报告了33名自闭症和巨头症患者的表型分类和基因测试评估。在我们的队列中，我们确认了PTEN突变与极端大头症(>；3SD，99.7%的ILE)的关联，并在22%的病例中发现了突变，包括三个新的PTEN突变。此外，我们定义了三个表型亚型：(1)与体细胞过度生长有关的病例，(2)不成比例的大头畸形病例，(3)与巨头畸形相关的病例。我们设计了一种新的方法来将患者分成这些亚组，这将有助于自闭症巨头症病例的分层。在这些亚组中，我们通过描述位于6q23.2和10q24.32的两个新的疑似致病拷贝数变异(CNV)，进一步扩展了患有大头畸形的自闭症病例的遗传病因。这些发现证明了与巨头症相关的自闭症病例的表型异质性及其遗传病因。在这个队列中，PTEN突变分析的临床收益率为22%，染色体微阵列(CMA)测试的临床收益率为9%。在巨头症自闭症患者中识别三个不同的表型亚群可能允许识别他们各自的不同的遗传病因，这些至今仍难以捉摸。
An association between autism and large head size has been previously described. Historically a subset of these cases have been correlated with mutations in the gene phosphatase and tensin homolog (PTEN). However, for the majority of cases the etiology is not known. We have studied 33 patients with autism and large head size. Within this group, we confirm the association of PTEN mutations and extreme head size and identify mutations in 22% of cases, including three novel PTEN mutations. In addition we define three novel phenotypic subgroups: (1) cases associated with somatic overgrowth (2) those with disproportionate macrocephaly and (3) those with relative macrocephaly. Members of these subgroups lack changes in the PTEN gene and furthermore we report two novel copy number changes in these patients. An association between autism and macrocephaly has been previously described. A subset of cases with extreme macrocephaly (>3SD, 99.7th %ile) have been correlated to mutations in the gene phosphatase and tensin homolog (PTEN). However, the phenotypic and genetic characterization of the remaining cases remains unclear. We report the phenotypic classification and genetic testing evaluation of a cohort of 33 patients with autism and macrocephaly. Within our cohort, we confirm the association of PTEN mutations and extreme macrocephaly (> 3SD, 99.7th %ile) and identify mutations in 22% of cases, including three novel PTEN mutations. In addition we define three phenotypic subgroups: (1) those cases associated with somatic overgrowth, (2) those with disproportionate macrocephaly, and (3) those will relative macrocephaly. We have devised a novel way to segregate patients into these subgroups that will aide in the stratification of autism macrocephaly cases. Within these subgroups, we further expand the genetic etiologies for autism cases with macrocephaly by describing two novel suspected pathogenic Copy Number Variants (CNVs) located at 6q23.2 and 10q24.32. These findings demonstrate the phenotypic heterogeneity of autism cases associated with macrocephaly and their genetic etiologies. The clinical yield from PTEN mutation analysis is 22% and 9% from Chromosomal Microarray (CMA) testing within this cohort. The identification of three distinct phenotypic subgroups within macrocephaly autism patients may allow for the identification of their respective distinct genetic etiologies which to date have remained elusive.
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影响因子：
3.7
作者：
Bruining H;de Sonneville L;Swaab H;de Jonge M;Kas M;van Engeland H;Vorstman J
通讯作者：
Vorstman J
DOI：
10.1097/gim.0b013e3181f8baad
发表时间：
2010-11
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Manning M;Hudgins L;Professional Practice and Guidelines Committee
通讯作者：
Professional Practice and Guidelines Committee
DOI：
10.1002/ajmg.b.30729
发表时间：
2008-10-05
影响因子：
2.8
作者：
Kent, Lindsey;Bowdin, Sarah;Maher, Eamonn R.
通讯作者：
Maher, Eamonn R.
影响因子：
8.8
作者：
Rosenfeld, Jill A.;Ballif, Blake C.;Shaffer, Lisa G.
通讯作者：
Shaffer, Lisa G.
影响因子：
3.7
作者：
Hu VW;Addington A;Hyman A
通讯作者：
Hyman A