{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T16:57:11Z","timestamp":1773075431537,"version":"3.50.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012940","name":"Universit\u00e4tsklinikum T\u00fcbingen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012940","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Funct Integr Genomics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mulvihill-Smith Syndrome (MSS) is a clinically complex and genetically unsolved nano-rare disorder with only 12 patients reported in the literature. Most patients (91%) have immunological impairments, succumb to infection, and might develop cancer later in life. Its pathogenesis remains elusive and therapeutic options are limited. We used single-cell MULTI-omics (sc-MULTI-omics), combining transcriptomics (gene expression, TCR, and BCR repertoire) and proteogenomic (Cellular Indexing of Transcriptomes and Epitopes by Sequencing; CITE-seq), to decipher the pathophysiology of nano-rare disease patient. We report a new patient who is a 16-year-old girl. She had an increased leukocyte counts and typical manifestations of MSS such as short stature, older appearance, multiple pigmented nevi, microcephaly, monolateral keratoconus, Marcus-Gunn syndrome, hearing loss, vitamin D deficiency, mild hypercortisolism, and diabetes mellitus with very high insulin resistance (T3DM). sc-MULTI-omics CITE-seq showed that the MSS patient had increased central memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells as well as effector memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, whilst reduced na\u00efve T cells (both CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells). Furthermore, we identified genes and pathways associated with the progeria-like phenotype, inflammation, and cancer progression, which may contribute to the clinical signs of MSS. sc-MUTLI-omics CITE-seq analyses improve our understanding of complex human disease pathophysiology and provides an alternative approach in personalized medicine in nano-rare disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s10142-025-01608-y","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:25:48Z","timestamp":1746750348000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["sc-MULTI-omics approach in nano-rare diseases: understanding the pathophysiological mechanism of Mulvihill-Smith Syndrome"],"prefix":"10.1007","volume":"25","author":[{"given":"Angelika","family":"Riess","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiana","family":"Roggia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje Schulze","family":"Selting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladislav","family":"Lysenkov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ossowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Casadei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-1369","authenticated-orcid":false,"given":"Olaf","family":"Riess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6919-6273","authenticated-orcid":false,"given":"Yogesh","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"1608_CR1","first-page":"e4735","volume":"13","author":"M Andreatta","year":"2023","unstructured":"Andreatta M, Gueguen P, Borcherding N, Carmona SJ (2023) T cell clonal analysis using single-cell RNA sequencing and reference maps. 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This study was performed under Institutional ethic (635\/2014BO1). The study procedures were carried out in accordance with Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All the authors read the manuscript and edited the manuscript. Further all the authors have given the consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"101"}}