{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:46:10Z","timestamp":1791852370506,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    CHIME syndrome is a variable condition characterized by ichthyosiform dermatosis, accompanied by intellectual disability, ocular colobomas, ear anomalies, and heart defects. It is an autosomal recessive condition caused by biallelic pathogenic variants in the\n                    <jats:italic>PIGL<\/jats:italic>\n                    gene. Until now, all reports of individuals affected with CHIME syndrome showed the\n                    <jats:italic>PIGL<\/jats:italic>\n                    c.500T&gt;C p.Leu167Pro DNA variant on one allele of the\n                    <jats:italic>PIGL<\/jats:italic>\n                    gene, in combination with another\n                    <jats:italic>PIGL<\/jats:italic>\n                    DNA variant on the other allele. This has led to the hypothesis that the p.Leu167Pro variant determines to a mild phenotypic effect only and that the core phenotype is determined by the second\n                    <jats:italic>PIGL<\/jats:italic>\n                    DNA variant. We report the first individual with CHIME syndrome, a 6\u2010year\u2010old girl, with homozygous\n                    <jats:italic>PIGL<\/jats:italic>\n                    p.Leu167Pro variants, defusing this hypothesis as she is not mildly affected. As CHIME is a very rare condition, it is expected that a significant proportion of cases will be due to homozygous gene variants, especially of founder DNA variants, and offspring of consanguineous parents. We speculate that the lack of homozygous p.Leu167Pro DNA variants so far has been due to chance and that other homozygous cases will be identified in future reports of affected individuals.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63962","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T05:11:32Z","timestamp":1733461892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>CHIME<\/scp>\n                    Syndrome in a Child With Homozygous\n                    <scp>\n                      <i>PIGL<\/i>\n                      p.Leu167Pro\n                    <\/scp>\n                    Variant"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3846-1596","authenticated-orcid":false,"given":"Eszter Sara","family":"Arany","sequence":"first","affiliation":[{"name":"Northwest Thames Regional Genetics Service Northwick Park &amp; St Mark's Hospitals  London UK"},{"name":"Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Zocche","sequence":"additional","affiliation":[{"name":"Northwest Thames Regional Genetics Service Northwick Park &amp; St Mark's Hospitals  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemima E.","family":"Mellerio","sequence":"additional","affiliation":[{"name":"St John's Institute of Dermatology, Guy's &amp; St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Holder\u2010Espinasse","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department Guy's &amp; St Thomas' NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Cobben","sequence":"additional","affiliation":[{"name":"Northwest Thames Regional Genetics Service Northwick Park &amp; St Mark's Hospitals  London UK"},{"name":"Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20104685\u2010gmb\u20102017\u20100172"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.15648"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36987"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22347"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R063313"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38181"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.010"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.09.017"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14969"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971003)72:1<24::AID-AJMG5>3.0.CO;2-V"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.6.465"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525\u20101470.2001.018003252.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525\u20101470.1996.tb00702.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3390185"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001401\u2010z"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1988.01670080014008"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320150217"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320170324"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:34:45Z","timestamp":1765517685000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/ajmg.a.63962"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63962","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,6]]},"assertion":[{"value":"2024-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63962"}}