{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T06:40:06Z","timestamp":1756363206387,"version":"3.44.0"},"reference-count":22,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,7,16]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>An early adolescent male with Shashi-Pena syndrome (SPS), characterised by a novel heterozygous pathogenic variant (<jats:italic>p.Ser627Phefs<\/jats:italic>*22) in the <jats:italic>ASXL2<\/jats:italic> gene, presented with a spectrum of manifestations. These encompassed intellectual disability, severe scoliosis, unique facial dysmorphisms, congenital heart disease, recurrent infections and autoimmune cytopenia. Distinctively, this case revealed late-onset hypogammaglobulinaemia and autoimmune cytopenia, which had not been previously documented in SPS. To our knowledge, this is the first report clinically delineating immune system involvement in a patient with SPS, thereby accentuating the significance of evaluating for immunodeficiency in the presence of Additional Sex Combs-Like (<jats:italic>ASXL<\/jats:italic>) gene anomalies, particularly against a backdrop of recurrent infections and autoimmune presentations. The implications of this case encourage further investigation into the incidence and underlying mechanisms of immune dysregulation in <jats:italic>ASXL<\/jats:italic>-related syndromes, aiming to enrich the clinical understanding and enhance the therapeutic approaches for these complex conditions.<\/jats:p>","DOI":"10.1136\/bcr-2024-263643","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T18:05:18Z","timestamp":1754330718000},"page":"e263643","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Shashi-Pena syndrome with late-onset specific hypogammaglobinaemia and autoimmune cytopenia"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1190-2433","authenticated-orcid":false,"given":"Adnan","family":"Al Ali","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergy, Department of Paediatrics, McGill University Health Centre, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"},{"name":"Department of Pediatrics, College of Medicine and Health Sciences, University, Al Ain, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwag","family":"Saidalani","sequence":"additional","affiliation":[{"name":"Department of pediatrics, King Abdulaziz University Hospital, Jeddah, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi","family":"Yeganeh","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Specialised Medicine, McGill University Health Centre, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Russell","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Specialised Medicine, McGill University Health Centre, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Alizadehfar","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Paediatrics, McGill University Health Centre, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Noya","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Paediatrics, McGill University Health Centre, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"McCusker","sequence":"additional","affiliation":[{"name":"Division of Paediatric Allergy and Clinical Immunology, Department of Paediatrics, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-1419","authenticated-orcid":false,"given":"Bruce","family":"Mazer","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Paediatrics, McGill University Health Centre, Montreal Children\u2019s Hospital, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"2025082723273850000_18.8.e263643.1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.281"},{"key":"2025082723273850000_18.8.e263643.2","doi-asserted-by":"publisher","DOI":"10.1186\/gm405"},{"key":"2025082723273850000_18.8.e263643.3","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1097\/ACI.0000000000000218","article-title":"The autoimmune conundrum in common variable immunodeficiency disorders","volume":"15","author":"van de Ven","year":"2015","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"2025082723273850000_18.8.e263643.4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.14785\/lymphosign-2019-0013","article-title":"Primary antibody deficiency associated with ring chromosome 18","volume":"7","author":"Yeganeh","year":"2020","journal-title":"LymphoSign Journal"},{"key":"2025082723273850000_18.8.e263643.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.11.001"},{"key":"2025082723273850000_18.8.e263643.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70200-2"},{"key":"2025082723273850000_18.8.e263643.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.04.049"},{"key":"2025082723273850000_18.8.e263643.8","doi-asserted-by":"publisher","DOI":"10.1186\/ar4186"},{"key":"2025082723273850000_18.8.e263643.9","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.234"},{"key":"2025082723273850000_18.8.e263643.10","doi-asserted-by":"publisher","DOI":"10.1038\/ng.868"},{"key":"2025082723273850000_18.8.e263643.11","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62156"},{"key":"2025082723273850000_18.8.e263643.12","unstructured":"Balasubramanian M , Schirwani S . ASXL3-related disorder. In: Adam MP , Mirzaa GM , Pagon RA , et al , eds. GeneReviews. Seattle (WA): University of Washington, Seattle, 2004. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK563693\/"},{"key":"2025082723273850000_18.8.e263643.13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0004750","article-title":"Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx","volume":"4","author":"Baskind","year":"2009","journal-title":"PLoS One"},{"key":"2025082723273850000_18.8.e263643.14","first-page":"845","article-title":"Identification and characterization of ASXL2 gene in silico","volume":"23","author":"Katoh","year":"2003","journal-title":"Int J Oncol"},{"key":"2025082723273850000_18.8.e263643.15","doi-asserted-by":"crossref","first-page":"110154","DOI":"10.1016\/j.clim.2024.110154","article-title":"212 Human ASXL1 Deficiency Causes Epigenetic Dysfunction, Combined Immunodeficiency and EBV\u2013Associated Hodgkin Lymphoma","volume":"262","author":"Fu","year":"2024","journal-title":"Clin Immunol"},{"key":"2025082723273850000_18.8.e263643.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1566"},{"key":"2025082723273850000_18.8.e263643.17","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R066944"},{"key":"2025082723273850000_18.8.e263643.18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s40778-020-00168-0","article-title":"The Role of ASXL1\/2 and Their Associated Proteins in Malignant Hematopoiesis","volume":"6","author":"Zhang","year":"2020","journal-title":"Curr Stem Cell Rep"},{"key":"2025082723273850000_18.8.e263643.19","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms15429","article-title":"ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia","volume":"8","author":"Micol","year":"2017","journal-title":"Nat Commun"},{"key":"2025082723273850000_18.8.e263643.20","doi-asserted-by":"publisher","DOI":"10.1586\/14789450.2015.1033409"},{"key":"2025082723273850000_18.8.e263643.21","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1002\/art.42492","article-title":"Ezh2 Knockout in B Cells Impairs Plasmablast Differentiation and Ameliorates Lupus-like Disease in MRL\/lpr Mice","volume":"75","author":"Zheng","year":"2023","journal-title":"Arthritis Rheumatol"},{"key":"2025082723273850000_18.8.e263643.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.029"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2024-263643","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T06:27:50Z","timestamp":1756362470000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2024-263643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,4]]},"published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1136\/bcr-2024-263643"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2024-263643","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2025,8]]}}}