An 8.9 Mb 19p13 duplication associated with precocious puberty and a sporadic 3.9 Mb 2q23.3q24.1 deletion containing NR4A2 in mentally retarded members of a family with an intrachromosomal 19p-into-19q between-arm insertion
An 8.9 Mb 19p13 duplication associated with precocious puberty and a sporadic 3.9 Mb 2q23.3q24.1 deletion containing NR4A2 in mentally retarded members of a family with an intrachromosomal 19p-into-19q between-arm insertion
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DOI：
10.1038/ejhg.2008.261
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发表时间：
2009-07-01
影响因子：
5.2
通讯作者：
Houge, Gunnar
中科院分区：
文献类型：
--
作者：
Lybaek, Helle;Orstavik, Karen Helene;Houge, Gunnar
在一名5个月前进入青春期、身材矮小、手部异常和严重智力低下的2岁半女孩中，检测到一个8.9 Mb的间质19p13重复，包含215个预测基因。最初假设复制涉及kisspeptin受体基因，GPR54，已知刺激青春期诱导，但更精细的复制图谱排除了这种可能性。为了进一步了解基因型-表型的相关性，在皮肤成纤维细胞中测量了整体基因表达。整体表达模式与对照组非常相似，只有约25%的重复基因表达水平增加了1.3倍以上，没有明显的变化可以解释性早熟。先证者的母亲携带一个平衡的手臂间插入的重复节段，类似于中心周围倒置。在其他几个家庭成员中也发现了同样的插入，其中一个家庭失去了一个女儿，她患有严重的智力迟钝，10岁时就出现了月经初潮。另一个近亲严重智障，但既不是畸形也不是小头症。他的表型最初被认为是由19p- in19q插入引起的19号隐染色体失衡，但随后的array-CGH检测到2q23.3q24.1缺失3.9 mb。这种新型微缺失涉及7个基因，其中FMNL2是Rho-GTPases的调节因子，NR4A2是多巴胺能神经元分化的重要基因，可能是2q23q24微缺失综合征的关键基因。欧洲人类遗传学杂志（2009）17,904 -910；doi: 10.1038 / ejhg.2008.261;2009年1月21日在线发布
In a 2 and a half-year-old girl with onset of puberty before the age of 5 months, short stature, hand anomalies and severe mental retardation, an 8.9 Mb interstitial 19p13 duplication containing 215 predicted genes was detected. It was initially assumed that the duplication involved the kisspeptin receptor gene, GPR54, known to stimulate induction of puberty, but more refined duplication mapping excluded this possibility. In an attempt to further understand the genotype-phenotype correlation, global gene expression was measured in skin fibroblasts. The overall expression pattern was quite similar to controls, and only about 25% of the duplicated genes had an expression level that was increased by more than 1.3-fold, with no obvious changes that could explain the precocious puberty. The proband's mother carried a balanced between-arm insertion of the duplicated segment that resembled a pericentric inversion. The same insertion was found in several other family members, including one who had lost a daughter with severe mental retardation and menarche at the age of 10 years. Another close relative was severely mentally retarded, but neither dysmorphic nor microcephalic. His phenotype was initially ascribed to a presumed cryptic chromosome 19 imbalance caused by the 19p-into19q insertion, but subsequent array-CGH detected a 3.9-Mb deletion of 2q23.3q24.1. This novel microdeletion involves seven genes, of which FMNL2, a suggested regulator of Rho-GTPases, and NR4A2, an essential gene for differentiation of dopaminergic neurons, may be critical genes for the proposed 2q23q24 microdeletion syndrome. European Journal of Human Genetics (2009) 17, 904-910; doi:10.1038/ejhg.2008.261; published online 21 January 2009