Abstract：
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder, caused by germline variants in the serine/threonine kinase 11 (STK11) gene. However, mosaic variants in STK11 gene have been rarely described. A 25-year-old woman diagnosed with PJS due to multiple hamartomatous polyps in the gastrointestinal tract was referred to our clinic. In the molecular diagnosis, the patient was evaluated using the STK11 gene sequence analysis and multiplex ligation-dependent probe amplification (MLPA) method, which suggested no pathogenic variant to account for the clinical picture. Given that the clinical findings of the patient were consistent with those of PJS, the raw data from next-generation sequencing (NGS) were re-examined for mosaicism which led to the detection of a novel mosaic c.920 + 1G > T variant in STK11 gene with a rate of 23% (1860x). Deep read-level NGS was performed on buccal mucosa and polyp samples to determine mosaicism levels in other tissues. Variant frequencies were 29% (710x) and 31% (1301x), respectively. Mosaicism should be considered in cases with clear clinical diagnostic criteria, such as PJS, where the pathogenic variant cannot be detected by sequence analysis and MLPA methods. Identification of mosaicism in these patients is very important as it can have an impact on patient follow-up and genetic counseling for relatives.
摘要：
Peutz-Jeghers综合征（PJS）是一种常染色体显性疾病，由丝氨酸/苏氨酸激酶11（STK11）基因中的种系变体引起。然而,STK11基因中的马赛克变体很少被描述。一名25岁的女性因胃肠道中的多发性错构瘤息肉而被诊断为PJS，被转诊到我们的诊所。在分子诊断中，使用STK11基因序列分析和多重连接依赖性探针扩增（MLPA）方法对患者进行评估，这表明没有致病变异来解释临床表现。鉴于患者的临床表现与PJS一致，对来自下一代测序(NGS)的原始数据进行了镶嵌性重新检查,结果在STK11基因中检测到一个新的镶嵌性c.920+1G>T变异,比率为23%(1860x).对颊粘膜和息肉样品进行深读水平NGS以确定其他组织中的镶嵌水平。变异频率分别为29%(710x)和31%(1301x)，分别。临床诊断标准明确的病例应考虑镶嵌性,比如PJS，其中通过序列分析和MLPA方法无法检测到致病变体。在这些患者中识别镶嵌性非常重要，因为它可能对患者的随访和亲属的遗传咨询产生影响。
