{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:45:29Z","timestamp":1792899929361,"version":"4.5.0"},"reference-count":7,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T00:00:00Z","timestamp":1496361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1026891"],"award-info":[{"award-number":["1026891"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:label\/><jats:p>GMPPA encodes the GDP\u2010mannose pyrophosphorylase A protein (GMPPA). The function of GMPPA is not well defined, however it is a homolog of GMPPB which catalyzes the reaction that converts mannose\u20101\u2010phosphate and guanosine\u20105\u2032\u2010triphosphate to GDP\u2010mannose. Previously, biallelic mutations in <jats:italic>GMPPA<\/jats:italic> were reported to cause a disorder characterized by achalasia, alacrima, neurological deficits, and intellectual disability. In this study, we report a female proband with achalasia, alacrima, hypohydrosis, apparent intellectual disability, seizures, microcephaly, esotropia, and craniofacial dysmorphism. Exome sequencing identified a previously unreported homozygous c.853+1G&gt;A variant in <jats:italic>GMPPA<\/jats:italic> in the proband and her affected sister. Their unaffected parents were heterozygous, and unaffected brother homozygous wild type for this variant. Lymphoblast cells from the affected sisters showed complete loss of the GMPPA protein by Western blotting, and increased levels of GDP\u2010mannose in lymphoblasts on high performance liquid chromatography. Based on our findings and the previous report describing patients with an overlapping phenotype, we conclude that this novel variant in <jats:italic>GMPPA<\/jats:italic>, identified by exome sequencing in the proband and her affected sister, is the genetic cause of their phenotype and may expand the known phenotype of this recently described glycosylation disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38292","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T12:06:58Z","timestamp":1496405218000},"page":"2246-2250","source":"Crossref","is-referenced-by-count":10,"title":["A novel mutation in <i>GMPPA<\/i> in siblings with apparent intellectual disability, epilepsy, dysmorphism, and autonomic dysfunction"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1808-0646","authenticated-orcid":false,"given":"Wendy A.","family":"Gold","sequence":"first","affiliation":[{"name":"Genetic Metabolic Disorders Research Unit, Western Sydney Genetics Program The Children's Hospital at Westmead Sydney New South Wales Australia"},{"name":"Discipline of Child and Adolescent Health, Sydney Medical School University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nara","family":"Sobreira","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Wiame","sequence":"additional","affiliation":[{"name":"Welbio and de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Marbaix","sequence":"additional","affiliation":[{"name":"Welbio and de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Van Schaftingen","sequence":"additional","affiliation":[{"name":"Welbio and de Duve Institute Universit\u00e9 Catholique de Louvain Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Franzka","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Jena University Hospital Friedrich\u2010Schiller\u2010University Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa G.","family":"Riley","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Research Unit, Western Sydney Genetics Program The Children's Hospital at Westmead Sydney New South Wales Australia"},{"name":"Discipline of Child and Adolescent Health, Sydney Medical School University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Worgan","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Liverpool Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A.","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Jena University Hospital Friedrich\u2010Schiller\u2010University Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Research Unit, Western Sydney Genetics Program The Children's Hospital at Westmead Sydney New South Wales Australia"},{"name":"Discipline of Child and Adolescent Health, Sydney Medical School University of Sydney Sydney New South Wales Australia"},{"name":"Genetic Medicine, Sydney Medical School University of Sydney Sydney New South Wales Australia"},{"name":"Neurodevelopmental Genomics Research Group, Murdoch Childrens Research Institute, and Department of Paediatrics Melbourne Medical School, University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley C.","family":"Ad\u00e8s","sequence":"additional","affiliation":[{"name":"Discipline of Child and Adolescent Health, Sydney Medical School University of Sydney Sydney New South Wales Australia"},{"name":"Genetic Medicine, Sydney Medical School University of Sydney Sydney New South Wales Australia"},{"name":"Department of Clinical Genetics The Children's Hospital at Westmead Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70040-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05840.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.08.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-010-1222-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2000.01781.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"17943","DOI":"10.1016\/S0021-9258(17)46796-2","article-title":"GDP\u2010mannose pyrophosphorylase. Purification to homogeneity, properties, and utilization to prepare photoaffinity analogs","volume":"268","author":"Szumilo T.","year":"1993","journal-title":"The Journal of Biological Chemistry"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38292","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T06:02:21Z","timestamp":1696572141000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,2]]},"references-count":7,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1002\/ajmg.a.38292"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38292","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,2]]}}}