Microdeletion of the Down Syndrome Critical Region at 21q22
Microdeletion of the Down Syndrome Critical Region at 21q22
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DOI：
10.1002/ajmg.a.33228
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发表时间：
2010-04-01
影响因子：
2
通讯作者：
Kosaki, Kenjiro
中科院分区：
文献类型：
--
作者：
Fujita, Hideki;Torii, Chiharu;Kosaki, Kenjiro
唐氏综合征关键区域的概念意味着存在几个剂量敏感基因，当复制时导致异常表型。在假定的唐氏综合征关键区域的基因中，DYRK1A和SIM2被认为是特别重要的，因为它们在模式生物中枢神经系统的发育中起着关键作用。考虑到导致关键靶基因表达量改变的调控失衡往往会在单体和三体中产生表型效应，唐氏综合征关键区域的单倍不足预计与异常表型有关。我们报告了一例患有严重小头畸形、发育迟缓、尿道下裂和角膜混浊的患者，该患者具有跨越唐氏综合征关键区域的微缺失，包括DYRK1A和SIM2。表现为宫内发育迟缓，尿道下裂，角膜混浊，眉弓，睑裂上斜狭窄，小舌裂，鼻根突出，小柱短，中门牙突出，牙钉状，颌后，乳头发育不全，严重发育迟缓。他的g带核型正常，但阵列比较基因组杂交显示在21q22染色体上重新缺失3.97 Mb。该患者的极端小头症可能归因于DYRK1A的单倍不全，因为小鼠DYRK1A零突变的杂合子的脑大小严重减少。(C) 2010 Wiley-Liss, Inc。
The concept of the Down syndrome critical region implies the existence of several dosage-sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, DYRK1A and SIM2 are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including DYRK1A and SIM2. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G-banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97 Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of DYRK1A, since brain size is severely reduced in heterozygotes for the Dyrk1a null mutation in mice. (C) 2010 Wiley-Liss, Inc.