Roberts C, Daw S C, Halford S, Scambler P J
Molecular Medicine Unit, Institute of Child Health, London, UK.
Hum Mol Genet. 1997 Feb;6(2):237-45. doi: 10.1093/hmg/6.2.237.
Deletions within human chromosome 22q11 cause a wide variety of birth defects including the DiGeorge syndrome and velo-cardio-facial (Shprintzen) syndrome. Despite the positional cloning of several genes from the critical region, it is still not possible to state whether the phenotype is secondary to haploinsufficiency of one or more than one gene. In embryological studies phenocopies of these abnormalities are produced by a variety of actions which disrupt the contribution made by the cranial and cardiac neural crest to development. The TUPLE1/HIRA gene is related to WD40 domain transcriptional regulators and maps within the DiGeorge critical region. We have cloned the chick homologue of HIRA and conducted in situ expression analysis in early chick embryos. Hira is expressed in the developing neural plate, the neural tube, neural crest and the mesenchyme of the head and branchial arch structures. HIRA may therefore have a role in the haploinsufficiency syndromes caused by deletion of 22q11.
人类22号染色体q11区域的缺失会导致多种出生缺陷，包括迪格奥尔格综合征和心脏颜面综合征（施普林曾综合征）。尽管已从关键区域定位克隆了多个基因，但仍无法确定该表型是否继发于一个或多个基因的单倍剂量不足。在胚胎学研究中，这些异常的拟表型可由多种作用产生，这些作用会破坏颅神经嵴和心脏神经嵴对发育的贡献。TUPLE1/HIRA基因与WD40结构域转录调节因子相关，定位于迪格奥尔格关键区域内。我们克隆了鸡的HIRA同源物，并在鸡早期胚胎中进行了原位表达分析。Hira在发育中的神经板、神经管、神经嵴以及头部和鳃弓结构的间充质中表达。因此，HIRA可能在由22q11缺失引起的单倍剂量不足综合征中起作用。
