CDKN2A基因荷兰p16-Leiden始创变异体嵌合体的意外案例。

Case Reports in Genetics Pub Date : 2025-08-28 eCollection Date: 2025-01-01 DOI:10.1155/crig/6261903
M van der Meulen, J T van Wezel, D Terlouw, J Morreau, E M P Steeghs, R van Doorn, M E van Leerdam, A M Onnekink, M C de Ruiter, N van der Stoep, T P Potjer
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引用次数: 0

摘要

CDKN2A是家族性皮肤黑色素瘤的主要高危易感基因。在荷兰,CDKN2A致病性种系变异的大多数携带者携带一种独特的、人群特异性的创始人变异,c.225_243del,通常被称为p16-Leiden。几十年来,CDKN2A中这种独特的19个碱基对缺失被确定为一种生殖系变异。在这里,我们报告了p16-Leiden突变体嵌合体的一个例外的情况下,在爱尔兰男性与卡塔赫纳综合征并发诊断,但没有恶性肿瘤的历史。该变异首先通过食管远端基底腺息肉的靶向下一代测序(NGS)发现,变异等位基因频率(VAF)为40%。随后的分析还在患者的口腔拭子DNA (VAF 0.3%)中检测到该变异,而在其他多种组织样本中,包括血液、尿液、皮肤和近端胃肠道的其他一些样本中,该变异明显不存在。我们探索了几个可以解释这些有趣发现的假设。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An Unexpected Case of Somatic Mosaicism of the Dutch p16-<i>Leiden</i> Founder Variant in the <i>CDKN2A</i> Gene.

An Unexpected Case of Somatic Mosaicism of the Dutch p16-Leiden Founder Variant in the CDKN2A Gene.

CDKN2A is the primary high-risk predisposition gene for familial cutaneous melanoma. In the Netherlands, most carriers of pathogenic germline variants in CDKN2A harbor a unique, population-specific founder variant, c.225_243del, commonly referred to as p16-Leiden. For decades, this distinctive 19 base-pair deletion in CDKN2A had been identified exclusively as a germline variant. Here, we report an exceptional case of somatic mosaicism for the p16-Leiden variant in an Irish male with a concurrent diagnosis of Kartagener's syndrome but no history of malignancy. The variant was first identified through targeted next-generation sequencing (NGS) of a fundic gland polyp in the distal esophagus, showing a variant allele frequency (VAF) of 40%. Subsequent analysis also detected the variant in the patient's buccal swab DNA (VAF 0.3%), while it was notably absent in multiple other tissue samples, including blood, urine, skin, and several additional samples from the proximal gastrointestinal tract. We explore several hypotheses that could explain these intriguing findings.

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