Ellison J W, Wardak Z, Young M F, Gehron Robey P, Laig-Webster M, Chiong W
Department of Pediatrics, University of California, San Francisco 94143, USA.
Hum Mol Genet. 1997 Aug;6(8):1341-7. doi: 10.1093/hmg/6.8.1341.
The abnormalities seen in Turner syndrome (monosomy X) presumably result from haploinsufficiency of certain genes on the X chromosome. Gene dosage considerations lead to the prediction that the culpable genes escape X inactivation and have functional homologs on the Y chromosome. Among the genes with these characteristics are those residing in the pseudoautosomal regions (PAR) of the sex chromosomes. A pseudoautosomal location for a dosage-sensitive locus involved in stature has been suggested based on the analyses of patients with deletions of a specific segment of the short arm PAR; hemizygosity for this putative locus probably also contributes to the short stature in Turner individuals. We have isolated a gene from the critical deleted region that encodes a novel homeodomain-containing transcription factor and is expressed at highest levels in osteogenic cells. We have named the gene PHOG, for pseudoautosomal homeobox-containing osteogenic gene. Its deletion in patients with short stature, the predicted altered dosage in 45,X individuals, along with the nature of the encoded protein and its expression pattern, make PHOG an attractive candidate for involvement in the short stature of Turner syndrome. We have also found that the mouse homolog of PHOG is autosomal, which may help to explain the lack of a growth abnormality in mice with monosomy X.
特纳综合征（X单体型）中所见的异常大概是由X染色体上某些基因的单倍剂量不足所致。基因剂量的考量使得人们预测，有问题的基因逃避了X染色体失活，并且在Y染色体上有功能同源物。具有这些特征的基因包括位于性染色体假常染色体区域（PAR）的那些基因。基于对PAR短臂特定片段缺失患者的分析，有人提出与身高相关的剂量敏感基因座位于假常染色体区域；这个假定基因座的半合子状态可能也导致了特纳综合征患者身材矮小。我们从关键缺失区域分离出了一个基因，它编码一种新型含同源结构域的转录因子，并且在成骨细胞中表达水平最高。我们将该基因命名为PHOG，即含假常染色体同源框的成骨基因。它在身材矮小患者中的缺失、在45,X个体中预测的剂量改变，以及所编码蛋白质的性质及其表达模式，使得PHOG成为参与特纳综合征身材矮小的一个有吸引力的候选基因。我们还发现，PHOG的小鼠同源物是常染色体的，这可能有助于解释X单体型小鼠没有生长异常的原因。
