Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene
Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene
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DOI：
10.1136/jmg.2005.037556
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发表时间：
2006-06-01
影响因子：
4
通讯作者：
Schwartz, C. E.
中科院分区：
文献类型：
--
作者：
Lubs, H.;Abidi, F. E.;Schwartz, C. E.
背景：Golabi、Ito和Hall在1984年报道了一个家庭有X相关的智力迟钝（XLMR）、小头畸形、出生后生长缺陷和其他异常，包括房间隔缺损。方法：作为我们正在进行的XLMR研究的一部分，重新研究了这个家族，但没有发现与X染色体标记的显著联系。观察到极度矮小和小头畸形以及其他新的临床表现。最近在四种XLMR疾病（Renpenning， Hamel脑-口-心综合征，Sutherland-Haan和Porteous综合征）以及其他几个家族中报道了聚谷氨酰胺束结合蛋白1基因（PQBP1）突变。我们家族与这些PQBP1突变患者的临床相似性，特别是小头畸形、身材矮小和房间隔缺损的存在，促使了对该基因的检查。结果：在PQBP1中发现了一个错义突变，将WW结构域65位的保守酪氨酸残基改变为半胱氨酸（p.Y65C）。结论：这是在PQBP1中发现的第一个错义突变，也是该基因WW结构域的第一个突变。WW结构域通过与转录因子中的PPxY基序相互作用，在转录调控中发挥重要作用。p.Y65C突变可能影响PQBP1蛋白作为转录共激活因子的正常功能。
Background: Golabi, Ito, and Hall reported a family with X linked mental retardation (XLMR), microcephaly, postnatal growth deficiency, and other anomalies, including atrial septal defect, in 1984.Methods: This family was restudied as part of our ongoing study of XLMR, but significant linkage to X chromosome markers could not be found. Extreme short stature and microcephaly as well as other new clinical findings were observed. Mutations in the polyglutamine tract binding protein 1 gene (PQBP1) have recently been reported in four XLMR disorders (Renpenning, Hamel cerebro-palato-cardiac, Sutherland-Haan, and Porteous syndromes) as well as in several other families. The clinical similarity of our family to these patients with mutations in PQBP1, particularly the presence of microcephaly, short stature, and atrial septal defect, prompted examination of this gene.Results: A missense mutation in PQBP1 was identified which changed the conserved tyrosine residue in the WW domain at position 65 to a cysteine (p.Y65C).Conclusions: This is the first missense mutation identified in PQBP1 and the first mutation in the WW domain of the gene. The WW domain has been shown to play an important role in the regulation of transcription by interacting with the PPxY motif found in transcription factors. The p.Y65C mutation may affect the proper functioning of the PQBP1 protein as a transcriptional co-activator.