{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:16:35Z","timestamp":1759882595884,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2018JJB140029"],"award-info":[{"award-number":["2018JJB140029"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary spherocytosis (HS) is a chronic non\u2010immune hemolytic anemia caused by congenital defects in the erythrocyte membrane. Gene variations can lead to HS, and the <jats:italic>SPTB<\/jats:italic> gene variation is one of them. However, HS with cholangiolithiasis and extremely intrahepatic cholestasis had been rarely discussed as a phenotype caused by <jats:italic>SPTB<\/jats:italic> gene variation, and the pathogenic mechanism of this gene variation is still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data were collected, genetic analysis was carried out by high throughput sequencing and Sanger sequencing, and then pathogenic mechanism of gene variation was revealed by Western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two children were admitted because of severe jaundice and finally confirmed as HS complicated with cholangiolithiasis and severe intrahepatic cholestasis. After conservative treatments, symptoms of cholangiolithiasis and intrahepatic cholestasis relieved. Respectively, two novel heterozygous variations of <jats:italic>SPTB<\/jats:italic> gene, (NM_001024858.4: c.493_494insTG, p. Q165fs) and (NM_001024858.4: c.1715delT, p. L572X), were identified in these two families. Western blot analysis revealed that these two pathogenic variations all cause decreased protein expression of \u03b2\u2010spectrin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We have identified two novel <jats:italic>SPTB<\/jats:italic> variations in HS with cholangiolithiasis and intrahepatic cholestasis. Moreover, our study enhances current understanding of the phenotype and molecular mechanisms associated with <jats:italic>SPTB<\/jats:italic> variation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.70006","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T02:58:56Z","timestamp":1750733936000},"page":"450-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel <i>SPTB<\/i> Variations Cause Hereditary Spherocytosis With Cholangiolithiasis and Severe Intrahepatic Cholestasis"],"prefix":"10.1111","volume":"89","author":[{"given":"Lin\u2010Lin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Guilin Medical University  Guilin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadik","family":"Ali","sequence":"additional","affiliation":[{"name":"Guilin Medical University  Guilin 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