title: A lesson from a reported pathogenic variant in Peutz-Jeghers syndrome: a case report.
abstract: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by mucocutaneous hyperpigmentation, gastrointestinal (GI) hamartmatous polyps, and an increased risk of various malignancies. Pathogenic variants in the LKB1 tumor suppressor gene (also known as STK11) are the major cause of PJS. In this study, compound heterozygous variants of LKB1, c.890G > A/ c.1062C > G and del(exon1)/ c.1062C > G, were identified in two sporadic Chinese PJS cases respectively. Although all these three variants had been related to the autosomal dominant PJS in previous studies, all evidences collected in this study including de novo data, segregation data, population data, in-silico data, and functional data indicated that del(exon1) and c.890G > A are pathogenic in these two PJS families rather than c.1062C > G. This finding would contribute to genetic counseling for individuals carrying the variant c.1062C > G with or without PJS phenotypes. Moreover, this finding reminds genetic counselors that it is necessary to reevaluate the pathogenicity of reported variants in a known Mendelian disorder in order to avoid a misleading decision.
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Tan
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Xianda
authors.initials: X
authors.lastname: Wei
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Huang
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.
authors.forename: Haoxian
authors.initials: H
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China.|Hunan Jiahui Genetics Hospital, Changsha, Hunan, 410078, China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Liang
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China. wulingqian@sklmg.edu.cn.|Hunan Jiahui Genetics Hospital, Changsha, Hunan, 410078, China. wulingqian@sklmg.edu.cn.
authors.forename: Lingqian
authors.identifier: 0000-0002-2665-0242
authors.initials: L
authors.lastname: Wu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010580:Peutz-Jeghers Syndrome / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055815:Young Adult
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: Genetic counseling; LKB1; Pathogenicity; Peutz-Jeghers syndrome; Variant