A second hit somatic (p.R905W) and a novel germline intron-mutation of TSC2 gene is found in intestinal lymphangioleiomyomatosis: a case report with literature review

Bogyeong Han, Juhwan Lee, Yoon Jin Kwak, Hyun Young Kim, Kwang Hoon Lee, Yumi Shim, Hyunju Lee, Sung Hye Park

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs associated with germline mutations in TSC1 and TSC2, including exonic, intronic, or mosaic mutations. Gastrointestinal (GI) tract Lymphangioleiomyomatosis (LAM) is an extremely rare manifestation of TSC, with few reported cases. Herein, we aimed to determine the driver mutation, pathogenesis, and relationship of germline and somatic mutations of LAM through whole-genome sequencing (WGS) of the tumor and blood samples and whole transcriptome sequencing (WTS) analysis. Case presentation: A nine-year-old girl with a full-blown TSC presented with abdominal masses detected during a routine check-up. Resected intestinal masses were diagnosed as LAM by thorough pathological examination. Interestingly, the LAM presented a somatic TSC2 gene mutation in exon 24 (p.R905W, c.C2713T), and the patient had intron retention by a novel germline mutation in the intron region of TSC2 (chr16:2126489, C > G). Conclusion: Our case suggests that intron retention by a single nucleotide intronic mutation of TSC2 is sufficient to develop severe manifestations of TSC, but the development of LAM requires an additional somatic oncogenic mutation of TSC2.

Original languageEnglish
Article number83
JournalDiagnostic pathology
Volume16
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Germline mutation
  • Intron retention
  • Lymphangioleiomyomatosis
  • Perivascular epithelioid cell tumor (PEComa)
  • Somatic mutation
  • Tuberous sclerosis complex

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