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A rare subset of GISTs are classified as wild-type GIST (wtGIST) and these are frequently associated with germline variants that affect the function of cancer predisposition genes such as the\u00a0succinate dehydrogenase subunit genes (<jats:italic>SDHA, SDHB, SDHC, SDHD<\/jats:italic>) or <jats:italic>NF1<\/jats:italic>. However, despite this high heritability, familial clustering of wtGIST is extremely rare. Here, we report a mother\u2013son diad who developed wtGIST at age 66 and 34 years, respectively. Comprehensive genetic testing revealed germline truncating variants in both <jats:italic>SDHA<\/jats:italic> (c.1534C&gt;T (p.Arg512*)) and <jats:italic>PALB2<\/jats:italic> (c.3113G&gt;A (p.Trp1038*)) in both affected individuals. The mother also\u00a0developed breast ductal carcinoma in-situ at age 70 years. Immunohistochemistry and molecular analysis of the wtGISTs revealed loss of SDHB expression and loss of the wild-type <jats:italic>SDHA<\/jats:italic> allele in tumour material. No allele loss was detected at <jats:italic>PALB2<\/jats:italic> suggesting that wtGIST tumourigenesis was principally driven by succinate dehydrogenase deficiency. However, we speculate that the presence of multilocus inherited neoplasia alleles syndrome (MINAS) in this family might have contributed to the highly unusual occurrence of familial wtGIST. Systematic reporting of tumour risks and phenotypes in individuals with MINAS will facilitate the clinical interpretation of the significance of this diagnosis, which is becoming more frequent as strategies for genetic testing for hereditary cancer becomes more comprehensive.<\/jats:p>","DOI":"10.1038\/s41431-021-00862-5","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T02:04:24Z","timestamp":1618452264000},"page":"1139-1145","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-2298","authenticated-orcid":false,"given":"James","family":"Whitworth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth T.","family":"Casey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-1747","authenticated-orcid":false,"given":"Philip S.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Giger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Ezequiel","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlee S.","family":"Fernando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipe","family":"Taniere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NIHR BioResource","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eamonn R.","family":"Maher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"862_CR1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.4251\/wjgo.v5.i6.102","volume":"5","author":"A Rammohan","year":"2013","unstructured":"Rammohan A, Sathyanesan J, Rajendran K, Pitchaimuthu A, Perumal S-K, Srinivasan U, et al. 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