BACKGROUND Prolactinomas represent 46 to 66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma. OBJECTIVE We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas. MATERIALS AND METHODS A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically-negative patients. RESULTS 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context, and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18, was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas. CONCLUSION we did not identify any (likely) pathogenic variants in patients over 30 years of age, either in a familial or sporadic context, and in in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.

中文翻译：

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催乳素瘤的基因检测：一项队列研究。

背景催乳素瘤占垂体腺瘤的 46% 至 66%，但种系突变的患病率很大程度上未知。我们在此提出第一项针对泌乳素瘤遗传倾向的研究。目的 我们研究了一大群孤立性泌乳素瘤患者种系突变的患病率。材料和方法 结合 2003 年至 2020 年间转诊进行 MEN1、AIP 和 CDKN1B 基因检测的患者的遗传和临床数据进行了一项回顾性研究。SF3B1 在遗传阴性患者中进行了桑格测序。结果 506 例泌乳素瘤患者被纳入其中：80 例泌乳素微瘤（15.9%），378 例泌乳素大瘤（74.7%），48 例未知；49/506 在家庭环境中 (9.7%)。其中，14 例 (2.8%) 在 MEN1 或 AIP 中具有（可能的）致病性变异，而在 CDKN1B 中则没有。所有阳性患者均在 30 岁之前罹患泌乳素大瘤。30 岁以下孤立性泌乳素大瘤患者的种系突变患病率在散发病例中为 4% (11/258)，在家族病例中为 15% (3/20)。18 岁以下散发病例的患病率，男性为 15% (5/33)，女性为 7% (4/57)。在 264 名泌乳素大腺瘤患者中未发现 R625H SF3B1 种系突变。结论 我们没有在 30 岁以上的患者中发现任何（可能的）致病性变异，无论是在家族性还是散发性背景下，以及在我们的系列或文献中的散发性背景下。应特别关注年轻患者和家庭背景。