{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:48:53Z","timestamp":1791377333494,"version":"4.3.2"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Posterior fossa malformations are among the most diagnosed central nervous system (CNS) anomalies detected by ultrasound (US) in prenatal age. We identified the pathogenic gene mutation in a male fetus of 17\u00a0weeks of gestation with US suspicion of familial Dandy\u2013Walker spectrum malformation, using Next Generation Sequencing approach in prenatal diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing (WES) approach has been performed on fetal genomic DNA. After reads preprocessing, mapping, variant calling, and annotation, a filtering strategy based on allelic frequency, recessive inheritance, and phenotypic ontologies has been applied. A fetal magnetic resonance imaging (MRI) at 18\u00a0weeks of gestation has been performed. An in silico analysis of a potential causative missense variant in the fukutin protein has been carried out through a structural modeling approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a new homozygous missense mutation in fukutin gene (<jats:italic>FKTN<\/jats:italic>, NM_006731.2: c.898G&gt;A; NP_006722.2: p.Gly300Arg). Fetal MRI supported molecular findings. Structural modeling analyses indicated a potential pathogenetic mechanism of the variant, through a reduced activation of the sugar moieties, which in turn impairs transfer to dystroglycan and thus its glycosylation. These findings pointed to a redefinition of the US suspicion of recurrence of Dandy\u2013Walker malformation (DWM) to a muscular dystrophy\u2010dystroglycanopathy type A4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present case confirmed WES as a reliable tool for the prenatal identification of the molecular bases of early\u2010detected CNS malformations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1054","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T13:42:32Z","timestamp":1574430152000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prenatal whole exome sequencing detects a new homozygous fukutin <i>(FKTN)<\/i> mutation in a fetus with an ultrasound suspicion of familial Dandy\u2013Walker malformation"],"prefix":"10.1002","volume":"8","author":[{"given":"Alice","family":"Traversa","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Clinical Genomics San Giovanni Rotondo (FG) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0902-3757","authenticated-orcid":false,"given":"Silvia","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Paiardini","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \"A. Rossi Fanelli\" Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Giovannetti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Clinical Genomics San Giovanni Rotondo (FG) Italy"},{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Marchionni","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luce","family":"Genovesi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Guadagnolo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Torres","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Cytogenetics San Giovanni Rotondo (FG) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Paolacci","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Cytogenetics San Giovanni Rotondo (FG) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Mazza","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Bioinformatics San Giovanni Rotondo (FG) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Carella","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Medical Genetics San Giovanni Rotondo (FG) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-1234","authenticated-orcid":false,"given":"Viviana","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pizzuti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza Laboratory of Clinical Genomics San Giovanni Rotondo (FG) Italy"},{"name":"Department of Experimental Medicine Sapienza University of Rome Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14900"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5201"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.26.3319"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11534"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm212"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.02.017"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.053"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22932"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000346518.68110.60"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy032"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.33"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3484"}],"container-title":["Molecular Genetics &amp; 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