{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:07:56Z","timestamp":1761311276186,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Walker\u2013Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to \u03b1\u2010dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O\u2010mannosyltransferase 1 (<jats:italic>POMT1<\/jats:italic>), protein O\u2010mannosyltransferase 2 (<jats:italic>POMT2<\/jats:italic>), protein O\u2010mannose beta\u20101,2\u2010N acetylglucosaminyltransferase (<jats:italic>POMGNT1<\/jats:italic>), fukutin (<jats:italic>FKTN<\/jats:italic>), isoprenoid synthase domain\u2010containing protein (<jats:italic>ISPD<\/jats:italic>), and other genes. We report on a consanguineous family with four consecutive siblings affected by this condition with lethal outcome in three (still birth), and termination of the fourth pregnancy based on antenatal MRI identification of brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising brain anomalies in the form of lissencephaly, subcortical\/subependymal heterotopia, and cerebellar hypoplasia shared by all four siblings; microphthalmia in one sibling; and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy\u2010Walker malformation. Whole exome sequencing of the fetus revealed a highly conserved missense mutation in <jats:italic>POMT2<\/jats:italic> that is known to cause WWS with brain and eye anomalies.In conclusion, the heterogeneous clinical presentation in the four affected conceptions with POMT2 mutation expands the current clinical spectrum of <jats:italic>POMT2<\/jats:italic>\u2010associated WWS to include large cystic kidneys; and confirms intra\u2010familial variability in terms of brain, kidney, and eye anomalies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38393","type":"journal-article","created":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T08:14:04Z","timestamp":1502957644000},"page":"2697-2702","source":"Crossref","is-referenced-by-count":11,"title":["Cystic kidneys in fetal Walker\u2013Warburg syndrome with <i>POMT2<\/i> mutation: Intrafamilial phenotypic variability in four siblings and review of literature"],"prefix":"10.1002","volume":"173","author":[{"given":"Marwa M.","family":"Nabhan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Centre of Pediatric Nephrology &amp; Transplantation, Kasr Al Ainy School of Medicine Cairo University Cairo Egypt"},{"name":"Egyptian Group for Orphan Renal Diseases (EGORD) Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nour","family":"ElKhateeb","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centre of Pediatric Neurology &amp; Metabolic diseases, Kasr Al Ainy School of Medicine Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela A.","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungho","family":"Eun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar N.","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kasr Al Ainy School of Medicine Cairo University Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heon","family":"YungGee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts"},{"name":"Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-1973","authenticated-orcid":false,"given":"Neveen A.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Centre of Pediatric Nephrology &amp; Transplantation, Kasr Al Ainy School of Medicine Cairo University Cairo Egypt"},{"name":"Egyptian Group for Orphan Renal Diseases (EGORD) Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,17]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1549298"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02814"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr357"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320320213"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980305)76:2<107::AID-AJMG1>3.0.CO;2-Q"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.450"},{"volume-title":"Handbook of pediatric autopsy pathology","year":"2013","author":"Gilbert\u2010Barness E.","key":"e_1_2_5_8_1"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm212"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2011.02.001"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.4052\/tigg.26.41"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.11.001"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.271767"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307228101"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2006.03.016"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00837"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02185752"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08316"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-282X2009000100038"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp369"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/0886022X.2014.883996"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.05.004"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.031963"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-1-29"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.01.001"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.6.831"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000268489.60809.c4"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00070-3"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1180512"}],"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.38393","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38393","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.38393","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38393","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T22:32:44Z","timestamp":1693348364000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,17]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1002\/ajmg.a.38393"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38393","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2017,8,17]]}}}