{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:14:07Z","timestamp":1785500047169,"version":"3.56.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T00:00:00Z","timestamp":1594771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["GeNeRARe"],"award-info":[{"award-number":["GeNeRARe"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["FKZ: 01GM1902A"],"award-info":[{"award-number":["FKZ: 01GM1902A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu\u2013Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre\u2010 or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease\u2010causing variants in the <jats:italic>PHGDH<\/jats:italic> and <jats:italic>PSAT1<\/jats:italic> genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest\u00a0that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at\u00a0the enzyme protein level.<\/jats:p>","DOI":"10.1002\/humu.24067","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T15:12:40Z","timestamp":1593011560000},"page":"1615-1628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders"],"prefix":"10.1155","volume":"41","author":[{"given":"Fatima","family":"Abdelfattah","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Kariminejad","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology and Genetics Center Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Karin","family":"Kahlert","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Genetik, Medizinische Fakult\u00e4t Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"},{"name":"Department of Congenital Heart Disease and Pediatric Cardiology University Hospital Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research and Cell Biology Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evren","family":"Gumus","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics School of Medicine, Harran University Sanliurfa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine D.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin W.","family":"Darbro","sequence":"additional","affiliation":[{"name":"Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Amor","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute Royal Children's Hospital Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne Melbourne Victoria Australia"},{"name":"Royal Children's Hospital Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maie","family":"Walsh","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute Royal Children's Hospital Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Sznajer","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique Humaine, Cliniques Universitaires Saint Luc Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Wei\u00df","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Klinische Genetik, Medizinische Fakult\u00e4t Carl Gustav Carus Technische Universit\u00e4t Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Weidensee","sequence":"additional","affiliation":[{"name":"Human Medical Genetics Erfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chitayat","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital University of Toronto Toronto Ontario Canada"},{"name":"Division of Clinical and Metabolic Genetics, The Hospital for SickKids University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Shannon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mount Sinai Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7282-2714","authenticated-orcid":false,"given":"Eva","family":"Bermejo\u2010S\u00e1nchez","sequence":"additional","affiliation":[{"name":"ECEMC (Spanish Collaborative Study of Congenital Malformations), Research Unit on Congenital Anomalies (UIAC), Institute of Rare Diseases Research (IIER), Institute of Health Carlos III, Ministry of Science and Innovation Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-5101","authenticated-orcid":false,"given":"Isolina","family":"Ria\u00f1o\u2010Gal\u00e1n","sequence":"additional","affiliation":[{"name":"AGC de Pediatr\u00eda Hospital Universitario Central de Asturias Oviedo Spain"},{"name":"IUOPA\u2010Departamento de Medicina\u2010ISPA Universidad de Oviedo Oviedo Spain"},{"name":"CIBER de Epidemiologia y Salud P\u00fablica Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Hayes","sequence":"additional","affiliation":[{"name":"Genetic Health Service New Zealand Auckland Hospital Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Poke","sequence":"additional","affiliation":[{"name":"Genetic Health Service New Zealand, Wellington Regional Hospital Wellington New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Rooryck","sequence":"additional","affiliation":[{"name":"MRGM INSERM U1211, CHU de Bordeaux, Service de G\u00e9n\u00e9tique M\u00e9dicale University of Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Pennamen","sequence":"additional","affiliation":[{"name":"MRGM INSERM U1211, CHU de Bordeaux, Service de G\u00e9n\u00e9tique M\u00e9dicale University of Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suonavy","family":"Khung\u2010Savatovsky","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de F\u0153topathologie H\u00f4pital Universitaire Robert\u2010Debr\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Toutain","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU de Tours, UMR 1253, iBrain Universit\u00e9 de Tours, INSERM Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-972X","authenticated-orcid":false,"given":"Marie\u2010Laure","family":"Vuillaume","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, CHU de Tours, UMR 1253, iBrain Universit\u00e9 de Tours, INSERM Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siavash","family":"Ghaderi\u2010Sohi","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology and Genetics Center Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad H.","family":"Kariminejad","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology and Genetics Center Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6nke","family":"Weinert","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Internal Medicine University Hospital Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Sticht","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-9269","authenticated-orcid":false,"given":"Martin","family":"Zenker","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denny","family":"Schanze","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Magdeburg Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3230365"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513815.2011.618864"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61076"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2015.10.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2015_510"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1470.2003.03017.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61559"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(00)00009-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513811003620914"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320130414"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440219"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/15513818609068856"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9921-5"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320130415"},{"issue":"1","key":"e_1_2_8_17_1","first-page":"312","article-title":"An essential role for de novo biosynthesis of l\u2010serine in CNS development","volume":"17","author":"Furuya S.","year":"2008","journal-title":"Asia Pacific Journal of Clinical Nutrition."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.12.009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150181505"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/517888"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17373"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2506"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-199710000-00004"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.74.6.542"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(95)00025-p"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320280104"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/316886"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2788.1972.tb01585.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20467"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36930"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.1526"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-3-52"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.04.011"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320350110"},{"issue":"3","key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1542\/peds.47.3.610","article-title":"A lethal syndrome of microcephaly with multiple congenital anomalies in three siblings","volume":"47","author":"Neu R. L.","year":"1971","journal-title":"Pediatrics"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2019.3673"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320300308"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111419200"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0012162200001171"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38217"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320560225"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0968-0004(00)89080-5"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.04.015"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.485"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12227"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9249-5"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20934"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2006.01645.x"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.20.8379"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201083"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12445"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhumu.24067","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/humu.24067","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/humu.24067","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/humu.24067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T06:45:27Z","timestamp":1759473927000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/humu.24067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,15]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1002\/humu.24067"],"URL":"https:\/\/doi.org\/10.1002\/humu.24067","archive":["Portico"],"relation":{},"ISSN":["1059-7794"],"issn-type":[{"value":"1059-7794","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7,15]]},"assertion":[{"value":"2020-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}