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.
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The authors are thankful for the participation of the patients, their families, their clinicians and volunteers in this study. This study was supported by grants from the National Key Basic Research Program of China (2012CB944600), the National Natural Science Foundation of China (81270706) and The National Key Technology R&D Program of China (2012BAI09B05).
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Conflict of interest
All authors declare that they have no conflict of interest.
Cosegregation analysis in the PJS families. (A) Variant c.890G>A was de novo in family 1. (B) Variant c.1062C>G was paternal in family 1. (C) Variant c.1062C>G was paternal in family 2. (D) Variant del(exon1) was de novo in family 2. Arrows indicate the variant sites. (TIF 1794 KB)
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