{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:11:26Z","timestamp":1792782686808,"version":"4.5.0"},"reference-count":5,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Zagazig University","id":[{"id":"https:\/\/ror.org\/053g6we49","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Two male siblings, aged 15 and 13\u00a0years, born to consanguineous parents, presented with hereditary anemia and thrombocytopenia associated with unexplained hepatosplenomegaly. Both were initially diagnosed with hereditary cytopenia and maintained on transfusion therapy since childhood. At age 15, the elder sibling developed acute thrombotic microangiopathy (TMA) with hypertensive encephalopathy, hemolytic anemia, severe thrombocytopenia, and acute kidney injury requiring hemodialysis and plasma exchange. The younger sibling exhibited predominantly hematological manifestations with severe anemia and thrombocytopenia but preserved kidney function, responding favorably to plasma transfusion. Whole-exome sequencing identified two distinct pathogenic variants: a homozygous mutation in\n                    <jats:italic>ADAMTS13<\/jats:italic>\n                    associated with hereditary thrombotic thrombocytopenic purpura (TTP; OMIM 274150), and a homozygous 57.1\u00a0Kb deletion at 1q31.3 involving\n                    <jats:italic>CFHR1<\/jats:italic>\n                    and\n                    <jats:italic>CFHR3<\/jats:italic>\n                    , associated with atypical hemolytic uremic syndrome (aHUS; OMIM 235400). This case series highlights the phenotypic variability of TMA syndromes and underscores the importance of comprehensive genetic testing in hereditary cytopenia.\n                  <\/jats:p>","DOI":"10.1007\/s00467-026-07335-1","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T08:26:51Z","timestamp":1778488011000},"page":"3891-3893","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual pathogenic variants in ADAMTS13 and CFHR1\/CFHR3 deletion: divergent thrombotic microangiopathy phenotypes in siblings"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1005-6046","authenticated-orcid":false,"given":"Mona Hamed","family":"Gehad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa M.","family":"Youssef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal S.","family":"El-Shal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona Mohammed","family":"Elsharkawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal E.","family":"Gohary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"7335_CR1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/art.42681","volume":"76","author":"J Leisring","year":"2024","unstructured":"Leisring J, Brodsky SV, Parikh SV (2024) Clinical evaluation and management of thrombotic microangiopathy. Arthritis Rheumatol 76:153\u2013165","journal-title":"Arthritis Rheumatol"},{"key":"7335_CR2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1182\/blood.2022015583","volume":"141","author":"A Doreille","year":"2023","unstructured":"Doreille A, Rafat C, Rondeau E, Mesnard L (2023) How I treat thrombotic microangiopathy in the era of rapid genomics. Blood 141:147\u2013155","journal-title":"Blood"},{"key":"7335_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1525062","volume":"11","author":"Y Huang","year":"2025","unstructured":"Huang Y, Zhou L, Song Y, Zou W, Tang A, Tao S, Tang D (2025) A compound heterozygous ADAMTS13 mutation causes congenital thrombotic thrombocytopenic purpura: a case report. Front Med 11:1525062","journal-title":"Front Med"},{"key":"7335_CR4","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1093\/ckj\/sfy010","volume":"11","author":"M Michael","year":"2018","unstructured":"Michael M, Turner N, Elenberg E, Shaffer LG, Teruya J, Arar M, Hui S-K, Smith RJ, Moake J (2018) Deficiency of complement factor H-related proteins and autoantibody-positive hemolytic uremic syndrome in an infant with combined partial deficiencies and autoantibodies to complement factor H and ADAMTS13. Clin Kidney J 11:791\u2013796","journal-title":"Clin Kidney J"},{"key":"7335_CR5","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1007\/s00467-018-3957-8","volume":"33","author":"M Bitzan","year":"2018","unstructured":"Bitzan M, Hammad RM, Bonnefoy A, Al Dhaheri WS, V\u00e9zina C, Rivard G-\u00c9 (2018) Acquired thrombotic thrombocytopenic purpura with isolated CFHR3\/1 deletion\u2014rapid remission following complement blockade. Pediatr Nephrol 33:1437\u20131442","journal-title":"Pediatr Nephrol"}],"container-title":["Pediatric Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-026-07335-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00467-026-07335-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-026-07335-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:34:42Z","timestamp":1790264082000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00467-026-07335-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,11]]},"references-count":5,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["7335"],"URL":"https:\/\/doi.org\/10.1007\/s00467-026-07335-1","relation":{},"ISSN":["0931-041X","1432-198X"],"issn-type":[{"value":"0931-041X","type":"print"},{"value":"1432-198X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,11]]},"assertion":[{"value":"19 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Written informed consent for publication of their clinical details was obtained from the patients\u2019 legal guardians. A copy of the consent form is available for review by the Editor of this journal.","order":1,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}