The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.
The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.
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DOI：
10.1210/jcem.83.9.5142
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发表时间：
1998-09
期刊：
影响因子：
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通讯作者：
J. Cogan;W. Wu;J. Phillips;I. Arnhold;A. Agapito;O. Fofanova;M. G. Osorio;İ. Bircan;A. Moreno;B. Mendonca
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文献类型：
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作者：
J. Cogan;W. Wu;J. Phillips;I. Arnhold;A. Agapito;O. Fofanova;M. G. Osorio;İ. Bircan;A. Moreno;B. Mendonca
联合垂体激素缺乏症 (CPHD) 的发病率约为 8000 名新生儿中就有 1 人。尽管家族性 CPHD 病例的比例尚不清楚，但约 10% 的患者有一级亲属受影响。我们最近报道了 PROP1 基因的三种突变，这些突变导致人类受试者出现 CPHD。我们在此报告了其中一种突变（PROP1 外显子 2 中的 301-302delAG 缺失）在 10 个独立确定的 CPHD 亲属和来自 8 个不同国家的 21 个散发性 CPHD 病例中的频率。我们的结果表明，在家族性 CPHD 病例中，55%（20 个中的 11 个）PROP1 等位基因具有 301-302delAG 缺失。有趣的是，尽管我们的 21 名散发病例中只有 12%（42 名中的 5 名）PROP1 等位基因为 301-302delAG，但在患有垂体和下丘脑缺陷的 CPHD 病例中，该等位基因的频率（在接受 TRH 刺激测试的 21 名散发受试者中的 20 名中）分别为 50%（6 名中的 3 名）和 0%（34 名中的 0 名）。利用全基因组辐射杂交分析，我们将PROP1基因定位于染色体5q的远端，并鉴定出紧密连锁的多态性标记D5S408，其可用于分离研究。对具有 301-302delAG 缺失的受影响受试者中的该标记进行的分析表明，301-302delAG 可能是一种反复出现的突变，而不是从共同创始人遗传的。
Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301-302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301-302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301-302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301-302delAG deletion suggests that rather than being inherited from a common founder, the 301-302delAG may be a recurring mutation.