{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:31:00Z","timestamp":1788503460514,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microcephalic osteodysplastic primordial dwarfism type I (MOPDI) is a very rare and severe autosomal recessive disorder characterized by marked intrauterine growth retardation, skeletal dysplasia, microcephaly and brain malformations. MOPDI is caused by biallelic mutations in <jats:italic>RNU4ATAC<\/jats:italic>, a non\u2010coding gene involved in U12\u2010type splicing of 1% of the introns in the genome, which are recognized by their specific splicing consensus sequences. Here, we describe a unique observation of immunodeficiency in twin sisters with mild MOPDI, who harbor a novel n.108_126del mutation, encompassing part of the U4atac snRNA 3\u2032 stem\u2010loop and Sm protein binding site, and the previously reported n.111G&gt;A mutation. Interestingly, both twin sisters show mild B\u2010cell anomalies, including low naive B\u2010cell counts and increased memory B\u2010cell and plasmablasts counts, suggesting partial and transitory blockage of B\u2010cell maturation and\/or excessive activation of naive B\u2010cells. Hence, the localization of a mutation in stem II of U4atac snRNA, as observed in another <jats:italic>RNU4ATAC<\/jats:italic>\u2010opathy with immunodeficiency, that is, Roifman syndrome (RFMN), is not required for the occurrence of an immune deficiency. Finally, we emphasize the importance of considering immunodeficiency in MOPDI management to reduce the risk of serious infectious episodes.<\/jats:p>","DOI":"10.1111\/cge.14571","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T06:43:59Z","timestamp":1717569839000},"page":"476-482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["B\u2010cell immune deficiency in twin sisters expands the phenotype of <scp>MOPDI<\/scp>"],"prefix":"10.1111","volume":"106","author":[{"given":"Lucas W.","family":"Gauthier","sequence":"first","affiliation":[{"name":"Department of Genetics, Clinical Genetics Unit, Centre de R\u00e9f\u00e9rence Maladies Rares des Anomalies du D\u00e9veloppement Sud\u2010Est, Hospices Civils de Lyon Universit\u00e9 Claude Bernard Lyon 1  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Gossez","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard\u2010Lyon 1, CNRS, UMR5308, ENS Lyon  Lyon France"},{"name":"Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Malcus","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Viel","sequence":"additional","affiliation":[{"name":"Plateforme de Bioth\u00e9rapies et de production de MTI, H\u00f4pital Edouard Herriot, Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Monneret","sequence":"additional","affiliation":[{"name":"Immunology Laboratory, Hospices Civils de Lyon, Edouard Herriot Hospital  Lyon France"},{"name":"Equipe d'Accueil 7426, Pathophysiology of Injury\u2010Induced Immunosuppression, Universit\u00e9 Claude Bernard Lyon 1, Hospices Civils de Lyon \u2013 bioM\u00e9rieux, H\u00f4pital Edouard Herriot  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remy","family":"Bordonn\u00e9","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier, University of Montpellier, CNRS UMR5535  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Pons","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de Cytog\u00e9n\u00e9tique, Laboratoire de Biologie M\u00e9dicale, Centre hospitalier de Valence  Valence France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cabet","sequence":"additional","affiliation":[{"name":"Pediatric and Fetal Imaging Department, Femme\u2010M\u00e8re\u2010Enfant Hospital, Hospices Civils de Lyon, Claude Bernard Lyon 1 University  Lyon France"},{"name":"Institut NeuroMyoG\u00e8ne, CNRS UMR5292, INSERM U1028, Claude Bernard Lyon 1 University  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Delous","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS, Centre de Recherche en Neurosciences de Lyon CRNL U1028 UMR5292, Genetics of Neurodevelopment Team (GENDEV)  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-0160","authenticated-orcid":false,"given":"Sylvie","family":"Mazoyer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS, Centre de Recherche en Neurosciences de Lyon CRNL U1028 UMR5292, Genetics of Neurodevelopment Team (GENDEV)  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Putoux","sequence":"additional","affiliation":[{"name":"Department of Genetics, Clinical Genetics Unit, Centre de R\u00e9f\u00e9rence Maladies Rares des Anomalies du D\u00e9veloppement Sud\u2010Est, Hospices Civils de Lyon Universit\u00e9 Claude Bernard Lyon 1  Bron France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS, Centre de Recherche en Neurosciences de Lyon CRNL U1028 UMR5292, Genetics of Neurodevelopment Team (GENDEV)  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Edery","sequence":"additional","affiliation":[{"name":"Department of Genetics, Clinical Genetics Unit, Centre de R\u00e9f\u00e9rence Maladies Rares des Anomalies du D\u00e9veloppement Sud\u2010Est, Hospices Civils de Lyon Universit\u00e9 Claude Bernard Lyon 1  Bron France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, INSERM, CNRS, Centre de Recherche en Neurosciences de Lyon CRNL U1028 UMR5292, Genetics of Neurodevelopment Team (GENDEV)  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"499","article-title":"A new type of primordial dwarfism","volume":"124","author":"Majewski F","year":"1976","journal-title":"Monatsschr Kinderheilkd 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