Genetic drivers of Cushing's disease: Frequency and associated phenotypes.
Genetic drivers of Cushing's disease: Frequency and associated phenotypes.
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DOI：
10.1016/j.gim.2022.08.021
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发表时间：
2022-12
影响因子：
8.8
通讯作者：
Stratakis, Constantine A.
中科院分区：
文献类型：
--
作者：
Hernandez-Ramirez, Laura C.;Pankratz, Nathan;Lane, John;Faucz, Fabio R.;Chittiboina, Prashant;Kay, Denise M.;Beethem, Zachary;Mills, James L.;Stratakis, Constantine A.
Cushing’s disease (CD) is often explained by a single somatic sequence change. Germline defects, however, often go unrecognized. We aimed to determine the frequency and associated phenotypes of genetic drivers of CD in a large cohort. We studied 245 unrelated CD patients (139 females, 56.7%), including 230 pediatric (93.9%) and 15 adult patients (6.1%). Germline exome sequencing (ES) was performed in 184 patients; tumor ES was also done in 27 of them. Forty-three germline samples and 92 tumor samples underwent Sanger sequencing of specific genes. Rare variants of uncertain significance (VUS), likely pathogenic (LP) or pathogenic variants in CD-associated genes were identified. Germline variants (13 VUS, 8 LP, and 11 pathogenic) were found in 8/19 (42.1%) patients with positive family history and in 23/226 (10.2%) sporadic patients. Somatic variants (one LP and seven pathogenic) were found in 20 out of 119 tested individuals (16.8%); one of them had a coexistent germline defect. Altogether, variants of interest were identified at the germline level in 12.2% of patients, at the somatic level in 7.8%, and coexisting germline and somatic variants in 0.4%, accounting for one-fifth of the cohort. We report an estimate of the contribution of multiple germline and somatic genetic defects underlying CD in a single cohort.
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.ecl.2018.02.007
发表时间：
2018-06-01
影响因子：
4.5
作者：
Hernandez-Ramirez, Laura C.;Stratakis, Constantine A.
通讯作者：
Stratakis, Constantine A.