{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:30:20Z","timestamp":1790857820871,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease caused by variations in genes such as\n                      <jats:italic>CSF2RA<\/jats:italic>\n                      and\n                      <jats:italic>CSF2RB<\/jats:italic>\n                      , which disrupt granulocyte\u2010macrophage colony\u2010stimulating factor signaling and impair surfactant clearance. These defects lead to progressive surfactant accumulation in alveoli, resulting in respiratory dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We describe a 3\u2010year\u2010old girl with Turner syndrome who presented with recurrent cough and dyspnea and was diagnosed with hereditary PAP. Diagnostic evaluation included high\u2010resolution computed tomography (HRCT), lung biopsy, and whole\u2010exome sequencing of peripheral blood cells. The patient received anti\u2010inflammatory antibiotics and underwent therapeutic whole lung lavage via endobronchial endoscopy. A systematic literature review of\n                      <jats:italic>CSF2RA<\/jats:italic>\n                      \u2010associated hereditary PAP was performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HRCT demonstrated characteristic \u201ccrazy paving\u201d patterns, and bronchoalveolar lavage fluid showed positive Periodic acid\u2010Schiff staining. Genetic analysis identified a novel hemizygous variation in\n                      <jats:italic>CSF2RA<\/jats:italic>\n                      (NM_000402.4:c.200_204del, p.Asn67SerfsTer8), confirmed as a de novo pathogenic variant. Whole lung lavage resulted in marked clinical improvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We report the first documented case of hereditary PAP caused by the\n                      <jats:italic>CSF2RA<\/jats:italic>\n                      variant NM_000402.4:c.200_204del (p.Asn67SerfsTer8), expanding the genetic spectrum of this disease. Our findings reinforce that\n                      <jats:italic>CSF2RA<\/jats:italic>\n                      \u2010related PAP exhibits phenotypic heterogeneity and confirm whole lung lavage as the cornerstone therapy. This case highlights the importance of genetic testing in diagnosing rare PAP subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70158","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T07:50:44Z","timestamp":1764316244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Hereditary Pulmonary Alveolar Proteinosis Caused by a Novel Hemizygous Variation of the\n                    <i>CSF2RA<\/i>\n                    Gene Case Report and Literature Review"],"prefix":"10.1002","volume":"13","author":[{"given":"Qiang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatric Respiratory Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-3029","authenticated-orcid":false,"given":"Sufen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Respiratory Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6990-8901","authenticated-orcid":false,"given":"Gefei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Clinical Trial Center Zhuhai Center for Maternal and Child Health Care  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25336"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43469"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl\u20102017\u2010211076"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201012\u2010164004"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010014\u20100171\u2010z"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.168450.113"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200708\u20101271OC"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890\u2010017\u20100382\u2010x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080759"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010018\u20100846\u2010y"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00725\u20102024"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.25174"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/a\u20102233\u20101243"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232\u2010016\u20100014\u20105"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201002\u20100271OC"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100066\u20103"}],"container-title":["Molecular Genetics &amp; 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