1 22q11 deletion 2（综合症） (also known as digeorge syndrome) is the most common human chromosome（染色体） deletion syndrome, having an estimated incidence（影响，发生率） of at least one in 4,000 live births. it has a range of severity（严格，猛烈） but a multisystem impact, with symptoms that may include congenital（先天的，天生的） heart defects, immunologic and endocrine（内分泌的，激素的） abnormalities, 3（裂缝，龟裂） palate, gastrointestinal problems, and neuropsychiatric abnormalities. nearly three-quarters of patients identified with this deletion syndrome have cardiac defects, and research into the 4 biology of this 5 has uncovered new knowledge of biological processes in both congenital heart disease（先天性心脏病） and early 6 development.
in the may 2010 issue of experimental biology and medicine, jason z. stoller, m.d., of the children's hospital of philadelphia, 7 with jonathan a. epstein, m.d., scientific director of the penn cardiovascular institute of the university of pennsylvania, report on an important interaction of two proteins, ash2l and tbx1, during early mammalian（哺乳类） development. "in humans and other mammals, the heart is among the first organs to develop," said stoller. "greater knowledge of biological events that occur in the earliest stages of development helps us to better understand both normal and abnormal heart development."
in cell and animal studies, the researchers discovered that ash2l, a core 8 of a protein complex responsible for epigenetic 11, is absolutely essential to early embryogenesis; without this protein, mouse 13 did not survive past the first few days of 14.
the region of chromosome 22 that is most commonly lost in digeorge syndrome contains more than 30 12, among them the 9 for the transcription factor（转录因子） tbx1. the tbx family of nuclear transcription factor proteins shares a t-box, a 15 16 17 18 that 19 regulation of downstream genes. in 2005, epstein and stoller identified a domain within the tbx1 protein that, when not functioning properly, plays a key role in causing digeorge syndrome in a subset of patients.
the current study aimed to identify proteins that interact with tbx1 in a 20 important way that could shed light on the pathogenesis（发病机理） of digeorge syndrome. using a 21 and cell culture studies, the researchers 22 the ash2l protein as interacting with tbx1. they then generated ash2l knockout mice to further investigate the role of the ash2l protein. mouse embryos that did not express ash21 died early in gestation（怀孕，妊娠期） —demonstrating that the protein is necessary for early development.
"the crucial requirement of the ash2l protein", said stoller, "suggests that it likely acts to regulate many developmental genes in mammals. as part of a histone（组蛋白） methyltransferase（甲基转移酶） complex, it regulates gene transcription by epigenetic 23".
future clinical implications for children and adults with digeorge syndrome are yet unclear. these patients have a normal ash2l gene, but the loss of tbx1 may alter the interaction between ash2l and tbx1 and play a role in their disease, possibly by regulating downstream genes. stoller added, "the fact that patients with this 10 syndrome are missing a copy of the tbx1 gene suggests that reduced amounts of the tbx1 protein may have biological effects that cause different features of the disease. further research is needed to discover these specific mechanisms."
dr. steven r. goodman, editor-in-chief of experimental biology and medicine, said "stoller et al have demonstrated that protein ash2l is essential in early embryogenesis. ash2l interacts with the transcription factor tbx1 which resides in a 24 region commonly deleted in digeorge syndrome. this interesting study suggests possible mechanisms leading to congenital heart disease in digeorge syndrome."
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