{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:29:02Z","timestamp":1788568142181,"version":"build-2803163510"},"reference-count":22,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,14]]},"abstract":"<jats:p>\n                    Phaeochromocytoma and paraganglioma are highly heritable tumours; half of those associated with a germline mutation are caused by mutations in genes for Krebs\u2019s cycle enzymes, including\n                    <jats:italic>succinate dehydrogenase<\/jats:italic>\n                    (\n                    <jats:italic>SDH<\/jats:italic>\n                    ). Inheritance of\n                    <jats:italic>SDH<\/jats:italic>\n                    alleles is assumed to be Mendelian (probability of 50% from each parent). The departure from transmission of parental alleles in a ratio of 1:1 is termed transmission ratio distortion (TRD). We sought to assess whether TRD occurs in the transmission of\n                    <jats:italic>SDHB<\/jats:italic>\n                    pathogenic variants (PVs). This study was conducted with 41 families of a discovery cohort from Royal North Shore Hospital, Australia, and 41 families from a validation cohort from St. Bartholomew\u2019s Hospital, United Kingdom (UK). Inclusion criteria were a clinically diagnosed\n                    <jats:italic>SDHB<\/jats:italic>\n                    PV and a pedigree available for at least two generations. TRD was assessed in 575 participants with the exact binomial test. The transmission ratio for\n                    <jats:italic>SDHB<\/jats:italic>\n                    PV was 0.59 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.005) in the discovery cohort, 0.67 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) in the validation cohort, and 0.63 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) in the combined cohort. No parent-of-origin effect was observed. TRD remained significant after adjusting for potential confounders: 0.67 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) excluding families with incomplete family size data; 0.58 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) when probands were excluded. TRD was also evident for\n                    <jats:italic>SDHD<\/jats:italic>\n                    PVs in a cohort of 81 patients from 13 families from the UK. The reason for TRD of\n                    <jats:italic>SDHB<\/jats:italic>\n                    and\n                    <jats:italic>SDHD<\/jats:italic>\n                    PVs is unknown, but we hypothesize a survival advantage selected during early embryogenesis. The existence of TRD for\n                    <jats:italic>SDHB<\/jats:italic>\n                    and\n                    <jats:italic>SDHD<\/jats:italic>\n                    has implications for reproductive counselling, and further research into the heterozygote state.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0233","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T07:10:57Z","timestamp":1676358657000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":4,"title":["Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring"],"prefix":"10.1530","volume":"30","author":[{"given":"Dahlia F","family":"Davidoff","sequence":"first","affiliation":[{"name":"Cancer Genetics, Kolling Institute, Royal North Shore Hospital, St Leonards, New South Wales, Australia"},{"name":"University of Sydney, Camperdown, New South Wales, Australia"},{"name":"Department of Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-7583","authenticated-orcid":true,"given":"Eug\u00e9nie S","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK"},{"name":"Department of Endocrinology, St. Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana E","family":"Benn","sequence":"additional","affiliation":[{"name":"Cancer Genetics, Kolling Institute, Royal North Shore Hospital, St Leonards, New South Wales, Australia"},{"name":"University of Sydney, Camperdown, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuvanaa","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, St. Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Dorman","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, St. Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Royal Hobart Hospital, Hobart, Tasmania, Australia"},{"name":"School of Medicine, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3893-3116","authenticated-orcid":true,"given":"Scott A","family":"Akker","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK"},{"name":"Department of Endocrinology, St. Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-0368","authenticated-orcid":true,"given":"Roderick J","family":"Clifton-Bligh","sequence":"additional","affiliation":[{"name":"Cancer Genetics, Kolling Institute, Royal North Shore Hospital, St Leonards, New South Wales, Australia"},{"name":"University of Sydney, Camperdown, New South Wales, Australia"},{"name":"Department of Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Gland Surgery","first-page":"105","article-title":"Pheochromocytoma\/paraganglioma: recent updates in genetics, biochemistry, immunohistochemistry, metabolomics, imaging and therapeutic options","volume":"9","author":"Antonio","year":"2020","unstructured":"Antonio KValdez MMNMercado-Asis LTa\u00efeb DPacak K2020Pheochromocytoma\/paraganglioma: recent updates in genetics, biochemistry, immunohistochemistry, metabolomics, imaging and therapeutic options. 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(https:\/\/doi.org\/10.1111\/cen.13877)"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/30\/5\/ERC-22-0233.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/30\/5\/ERC-22-0233.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/30\/5\/ERC-22-0233.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:21Z","timestamp":1784555781000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/25731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":22,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/erc-22-0233","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]}}}