Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.
Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.
复制标题
合并垂体激素缺乏症儿童中 PROP-1 基因的复合杂合缺失。
DOI：
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发表时间：
1998
影响因子：
5.8
通讯作者：
S. Yamashita
中科院分区：
文献类型：
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作者：
O. Fofanova;N. Takamura;E. Kinoshita;J. Parks;M. Brown;V. Peterkova;O. Evgrafov;N. Goncharov;A. Bulatov;I. Dedov;S. Yamashita
Pit-1基因（PROP 1）的突变已被证明是导致垂体激素缺乏症（CPHD）与生长激素（GH）、催乳素（Prl）、促甲状腺激素（TSH）和促性腺激素缺乏症的原因。我们以前报道，纯合性的外显子2（296 delGA）的2bp缺失占CPHD在三个患者从两个俄罗斯家庭。在这里，我们报告了第二个突变热点外显子2。该2bp 149 delGA缺失导致移码，其导致相同的丝氨酸在密码子109处变为终止密码子（S109 X）。预测的蛋白质各自在残基108处截短，但在同源结构域中的不同点处与野生型序列不同。4个家系的14例CPHD患儿中有5例（36%）为149 delGA/296 delGA复合杂合。这提供了第一个证据的杂合性两个常见的缺失作为一个原因CPHD在俄罗斯儿童。
Mutations in the prophet of Pit-1 gene (PROP1) have been shown to be responsible for combined pituitary hormone deficiency (CPHD) with deficiencies of growth hormone (GH), Prolactin (Prl), thyroid-stimulating hormone (TSH) and gonadotropins. We previously reported that homozygosity for a 2bp deletion in exon 2 (296delGA) accounted for CPHD in three patients from two Russian families. Here we report a second mutational hot spot in exon 2. This 2bp 149delGA deletion results in a frame shift that leads to the same serine to stop codon change at codon 109 (S109X). The predicted proteins are each truncated at residue 108 but diverge from the wild type sequence at different points in the homeodomain. Compound heterozygosity for the two mutations (149delGA/296delGA) was detected in 5 of 14 CPHD children from 4 families (36%). This provides the first evidence of heterozygosity for two common deletions as a cause of CPHD in Russian children.