{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:03:34Z","timestamp":1790744614123,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hyperphosphatasia with mental retardation syndrome (<jats:styled-content style=\"fixed-case\">HPMRS<\/jats:styled-content>) is caused by recessive mutations in genes involved in the glycosylphosphatidylinsitol pathway, including <jats:italic><jats:styled-content style=\"fixed-case\">PGAP3<\/jats:styled-content><\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We describe 10 patients from 8 Egyptian families presenting with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Sanger sequencing of <jats:italic>PGAP3<\/jats:italic> was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight patients had cleft palate, 4 had postnatal microcephaly and 5 had seizures. Neuro\u2010imaging findings showed thin corpus callosum in 9 patients, mild ventriculomegaly in 3 patients and variable degrees of cerebellar vermis hypoplasia in 4 patients, a finding not previously reported in patients with <jats:styled-content style=\"fixed-case\">HPMRS<\/jats:styled-content>. Additional manifestations included double row teeth, hypogenitalism and congenital heart disease. Biallelic loss of function mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">PGAP3<\/jats:styled-content><\/jats:italic> gene were detected in all patients. Nine patients were homozygous for the c.<jats:styled-content style=\"fixed-case\">402dupC<\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">M135Hfs<\/jats:styled-content>*28) mutation strongly suggesting a founder effect. On the other hand, 1 patient had a novel mutation, c.817_820delGACT (p.<jats:styled-content style=\"fixed-case\">D273Sfs<\/jats:styled-content>*37).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the largest series of patients with <jats:styled-content style=\"fixed-case\">HPMRS<\/jats:styled-content> from same ethnic group. Our results reinforce the distinct clinical and facial features of <jats:italic><jats:styled-content style=\"fixed-case\">PGAP3<\/jats:styled-content><\/jats:italic>\u2010related <jats:styled-content style=\"fixed-case\">HPMRS<\/jats:styled-content> which are the clue for targeted genetic testing. Moreover, we present additional unreported clinical and neuro\u2010imaging findings and a novel mutation thus expanding the phenotypic and mutational spectrum of this rare disorder.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cge.13033","type":"journal-article","created":{"date-parts":[[2017,4,8]],"date-time":"2017-04-08T08:08:46Z","timestamp":1491638926000},"page":"84-91","source":"Crossref","is-referenced-by-count":27,"title":["<i><scp>PGAP3<\/scp><\/i>\u2010related hyperphosphatasia with mental retardation syndrome: Report of 10 new patients and a homozygous founder mutation"],"prefix":"10.1111","volume":"93","author":[{"given":"M.S.","family":"Abdel\u2010Hamid","sequence":"first","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics and Genome Research Division National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.Y.","family":"Issa","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Division National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.A.","family":"Otaify","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Division National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.F.","family":"Abdel\u2010Ghafar","sequence":"additional","affiliation":[{"name":"Medical Molecular Genetics Department, Human Genetics and Genome Research Division National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.M.","family":"Elbendary","sequence":"additional","affiliation":[{"name":"Child Health Department, Medical Research Division National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-0002","authenticated-orcid":false,"given":"M.S.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department, Human Genetics and Genome Research Division National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.01.004"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20121982"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231921"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.12.012"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvn090"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.10.024"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.90.130"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.007"},{"key":"e_1_2_6_10_1","first-page":"1227","article-title":"Inherited GPI deficiency; 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