{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:46:45Z","timestamp":1790322405892,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1798\/16"],"award-info":[{"award-number":["1798\/16"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1520\/09"],"award-info":[{"award-number":["1520\/09"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1798\/16"],"award-info":[{"award-number":["1798\/16"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1520\/09"],"award-info":[{"award-number":["1520\/09"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>Mutations in genes involved in the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor cause autosomal recessive glycosylation defects, with a wide phenotypic spectrum of intellectual disability, seizures, minor facial dysmorphism, hypotonia, and elevated serum alkaline phosphatase. We now describe consanguineous Bedouin kindred presenting with an autosomal recessive syndrome of intellectual disability and elevated serum alkaline phosphatase. Genome-wide linkage analysis identified 6 possible disease-associated loci. Whole-exome sequencing followed by Sanger sequencing validation identified a single variant in<jats:italic> PGAP2<\/jats:italic> as the disease-causing mutation (C.554G&gt;A; p.185(R&gt;Q)), segregating as expected within the kindred and not found in 150 Bedouin controls. The mutation replaces a highly conserved arginine residue with glutamine within the Frag1 (FGF receptor activating) domain of PGAP2. Interestingly, this mutation is a known dbSNP variant (rs745521288, build 147) with a very low allele frequency (0.00000824 in dbSNP, no homozygotes reported), highlighting the fact that dbSNP variants should not be automatically ruled out as disease-causing mutations. We further showed that<jats:italic> PGAP2<\/jats:italic> is ubiquitously expressed, but in line with the disease phenotype, it is highly transcribed in human brain, skeletal muscle, and liver. Interestingly, a mild phenotype of slightly elevated serum levels of alkaline phosphatase and significant learning disabilities was observed in heterozygous carriers.<\/jats:p>","DOI":"10.1155\/2017\/3470234","type":"journal-article","created":{"date-parts":[[2017,10,8]],"date-time":"2017-10-08T17:00:35Z","timestamp":1507482035000},"page":"1-7","source":"Crossref","is-referenced-by-count":14,"title":["A Rare Variant in<i> PGAP2<\/i> Causes Autosomal Recessive Hyperphosphatasia with Mental Retardation Syndrome, with a Mild Phenotype in Heterozygous Carriers"],"prefix":"10.1155","volume":"2017","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9791-1617","authenticated-orcid":true,"given":"Yonatan","family":"Perez","sequence":"first","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University of the Negev, 84105 Beer Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohad","family":"Wormser","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University of the Negev, 84105 Beer Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Sadaka","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Division of Pediatrics, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, 84101 Beer Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Birk","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Ariel University, Ariel, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginat","family":"Narkis","sequence":"additional","affiliation":[{"name":"Genetics Institute, Soroka University Medical Center, Ben Gurion University of the Negev, 84101 Beer Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1430-1296","authenticated-orcid":true,"given":"Ohad S.","family":"Birk","sequence":"additional","affiliation":[{"name":"The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben Gurion University of the Negev, 84105 Beer Sheva, Israel"},{"name":"Genetics Institute, Soroka University Medical Center, Ben Gurion University of the Negev, 84101 Beer Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.008"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.03.011"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2016.01.007"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.10.027"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp369"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx013"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1038\/hdy.2013.90"}],"container-title":["BioMed Research International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2017\/3470234.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2017\/3470234.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/bmri\/2017\/3470234.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,10,8]],"date-time":"2017-10-08T17:00:42Z","timestamp":1507482042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/bmri\/2017\/3470234\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":8,"alternative-id":["3470234","3470234"],"URL":"https:\/\/doi.org\/10.1155\/2017\/3470234","relation":{},"ISSN":["2314-6133","2314-6141"],"issn-type":[{"value":"2314-6133","type":"print"},{"value":"2314-6141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]}}}