{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:10:16Z","timestamp":1779912616816,"version":"3.53.1"},"reference-count":23,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI22\/01127"],"award-info":[{"award-number":["PI22\/01127"]}]},{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI22\/00272"],"award-info":[{"award-number":["PI22\/00272"]}]},{"name":"European Union","award":["PI22\/01127"],"award-info":[{"award-number":["PI22\/01127"]}]},{"name":"European Union","award":["PI22\/00272"],"award-info":[{"award-number":["PI22\/00272"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Germline variants in the phosphatidylinositol glycan class A (PIGA) gene, which is involved in glycosylphosphatidylinositol (GPI) biosynthesis, cause multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) with X-linked recessive inheritance. The available literature has described a pattern of almost 100% X-chromosome inactivation in mothers carrying PIGA variants. Here, we report a male infant with MCAHS2 caused by a novel PIGA variant inherited from his mother, who has a non-skewed pattern of X inactivation. Phenotypic evidence supporting the pathogenicity of the variant was obtained by flow-cytometry tests. We propose that the assessment in neutrophils of the expression of GPI-anchored proteins (GPI-APs), especially CD16, should be considered in cases with variants of unknown significance with random X-inactivation in carrier mothers in order to clarify the pathogenic role of PIGA or other gene variants linked to the synthesis of GPI-APs.<\/jats:p>","DOI":"10.3390\/genes15060802","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T05:27:19Z","timestamp":1718861239000},"page":"802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 Caused by a Novel PIGA Variant Not Associated with a Skewed X-Inactivation Pattern"],"prefix":"10.3390","volume":"15","author":[{"given":"Alba","family":"Gabaldon-Albero","sequence":"first","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Pediatric Neurology Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-3423","authenticated-orcid":false,"given":"Lourdes","family":"Cordon","sequence":"additional","affiliation":[{"name":"Hematology Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto Carlos III, 20029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Sempere","sequence":"additional","affiliation":[{"name":"Hematology Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Instituto Carlos III, 20029 Madrid, Spain"},{"name":"Hematology and Hemotherapy Service, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-6124","authenticated-orcid":false,"given":"Laia","family":"Pedrola","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-819X","authenticated-orcid":false,"given":"Carla","family":"Martin-Grau","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvestre","family":"Oltra","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Monfort","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Caro-Llopis","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Dominguez-Martinez","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hernandez-Muela","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rosello","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-5859","authenticated-orcid":false,"given":"Carmen","family":"Orellana","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Martinez","sequence":"additional","affiliation":[{"name":"Translational Genetics Research Group, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Genetics Unit, Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/jb\/mvn090","article-title":"Biosynthesis, remodelling and functions of mammalian GPI-anchored proteins: Recent progress","volume":"144","author":"Kinoshita","year":"2008","journal-title":"J. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ajhg.2011.11.031","article-title":"The phenotype of a germline mutation in PIGA: The gene somatically mutated in paroxysmal nocturnal hemoglobinuria","volume":"90","author":"Johnston","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/ajmg.a.36189","article-title":"A novel germline PIGA mutation in Ferro-Cerebro-Cutaneous syndrome: A neurodegenerative X-linked epileptic encephalopathy with systemic iron-overload","volume":"164","author":"Swoboda","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/ajmg.a.36184","article-title":"Expanding the spectrum of pheno-types associated with germline PIGA mutations: A child with developmental delay, acceler-ated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities","volume":"164","author":"Harakalova","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13023-015-0243-8","article-title":"The genotypic and phenotypic spectrum of PIGA deficiency","volume":"10","author":"Sinclair","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Furlan, G., and Galupa, R. (2022). Mechanisms of Choice in X-Chromosome Inactivation. 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