{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:36:26Z","timestamp":1788244586738,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol\u2010anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co\u2010receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the <jats:italic>PIGA<\/jats:italic> gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X\u2010exome sequencing in the proband identified a c.278C&gt;T (p.Pro93Leu) mutation in the <jats:italic>PIGA<\/jats:italic> gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X\u2010chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in <jats:italic>PIGA<\/jats:italic> support the determination that this mutation caused the phenotype in this family. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36184","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T00:37:13Z","timestamp":1384994233000},"page":"29-35","source":"Crossref","is-referenced-by-count":42,"title":["Expanding the spectrum of phenotypes associated with germline <i>PIGA<\/i> mutations: A child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities"],"prefix":"10.1002","volume":"164","author":[{"given":"Saskia N.","family":"van der Crabben","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Harakalova","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva H.","family":"Brilstra","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique M.C.","family":"van Berkestijn","sequence":"additional","affiliation":[{"name":"Department of Paediatrics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris C.","family":"Hofstede","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianus J.","family":"van Vught","sequence":"additional","affiliation":[{"name":"Department of Paediatric Intensive Care University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Cuppen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wigard","family":"Kloosterman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Kristian","family":"Ploos van Amstel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs","family":"van Haaften","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke M.","family":"van Haelst","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1410"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.396"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100921"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.031"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr073"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.653"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101654"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087114"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.331090"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1182\/blood.V86.12.4650.bloodjournal86124650","article-title":"Mutations 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