中国麻风皮肤病杂志 ›› 2026, Vol. 42 ›› Issue (4): 234-238.doi: 10.12144/zgmfskin202604234

• 论著 • 上一篇    下一篇

LEOPARD综合征PTPN11基因突变检测与文献分析

贾轲1,2,赵晴1,2,陈声利1,2,张帆1,2,刘红1,2   

  1. 1山东第一医科大学附属皮肤病医院，山东济南，250022；2山东省皮肤病性病防治研究所，山东济南，250022
  • 出版日期:2026-04-15 发布日期:2026-04-07

Mutation detection of PTPN11 gene in LEOPARD syndrome and literature review

JIA Ke1,2, ZHAO Qing1,2, CHEN Shengli1,2, ZHANG Fan1,2, LIU Hong1,2   

  1. 1 Dermatology Hospital of Shandong First Medical University, Jinan 250022, China; 2 Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan 250022, China
  • Online:2026-04-15 Published:2026-04-07

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摘要： 目的：报道1例因皮肤弥漫性黑色斑疹就诊，确诊为LEOPARD综合征的患者，对其进行基因突变检测并检索相关文献，总结该病基因突变位点及临床特征。方法：采用全外显子组测序方法对患者进行基因突变检测，在PubMed和Web of Science数据库中以(“LEOPARD syndrome” OR “Noonan syndrome with multiple lentigines” OR “NSML”) AND (PTPN11 OR RAF1 OR BRAF OR MAP2K1)为检索式，检索1964年至2025年10月所有报道具有明确基因突变位点并附有临床表型信息的文献，整理LEOPARD综合征的基因突变谱。结果：患者携带PTPN11基因7号外显子杂合突变（c.836A>G），根据ACMG变异分级，该突变被判定为致病性突变。文献检索共纳入81篇文献、154例患者，临床表现以多发性雀斑样痣为主要特征，常伴不同程度的心脏受累及感音神经性听力异常。PTPN11是最常见的致病基因，占全部病例的93.51%（144/154），其余少见致病基因包括RAF1、BRAF和MAP2K1，其中，RAF1基因突变与肥厚型心肌病的发生密切相关。结论：LEOPARD综合征虽罕见，但具有典型皮肤表现。早期基因学检测及心脏、听力等系统性评估有助于及时识别和综合管理。

关键词: LEOPARD综合征, PTPN11基因, 多发性雀斑样痣

Abstract: To report an 18-year-old male who presented with diffuse dark macules of the skin and was diagnosed with LEOPARD syndrome, and to perform genetic mutation analysis and a literature review to summarize the genetic mutation sites and clinical characteristics of this disorder. Methods: We performed whole-exome sequencing to identify genetic mutations in the patient. We conducted a systematic literature search in the PubMed and Web of Science databases using the following search strategy: (“LEOPARD syndrome” OR “Noonan syndrome with multiple lentigines” OR “NSML”) AND (PTPN11 OR RAF1 OR BRAF OR MAP2K1). We included publications from 1964 to October 2025 that reported cases or case series with clearly defined genetic mutation sites and corresponding clinical phenotypes to characterize the mutational spectrum of LEOPARD syndrome. Results: Genetic analysis identified a heterozygous mutation in exon 7 of the PTPN11 gene (c.836A>G), which met the ACMG criteria for pathogenicity. The literature review included a total of 81 publications comprising 154 patients. Most patients presented with multiple lentigines, frequently accompanied by varying degrees of cardiac involvement and sensorineural hearing impairment. PTPN11 was the most common causative gene, accounting for 93.51% of all cases (144/154), whereas other less frequent pathogenic genes included RAF1, BRAF, and MAP2K1. Notably, mutations in RAF1 showed a strong association with the development of hypertrophic cardiomyopathy. Conclusion: Although LEOPARD syndrome is rare, it shows distinctive cutaneous manifestations. Early genetic testing, together with systematic evaluations of the cardiovascular and auditory systems, facilitates timely diagnosis and comprehensive management.

Key words: LEOPARD syndrome, PTPN11 gene, multiple lentigines