{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:55:42Z","timestamp":1781578542702,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T00:00:00Z","timestamp":1532390400000},"content-version":"vor","delay-in-days":53,"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 C"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>Holoprosencephaly (HPE) has been defined as a distinct clinical entity with characteristic facial gestalt, which may\u2014or may not\u2014be associated with the true brain malformation observed postmortem in autopsy or in pre\u2010 or postnatal imaging. Affected families mainly show autosomal dominant inheritance with markedly reduced penetrance and extremely broad clinical variability even between mutation carriers within the same families. We here present advances in prenatal imaging over the last years, increasing the proportion of individuals with HPE identified prenatally including milder HPE forms and more frequently allowing to detect more severe forms already in early gestation. We report the results of diagnostic genetic testing of 344 unrelated patients for HPE at our lab in Germany since the year 2000, which currently with the application of next generation sequencing (NGS) panel sequencing identifies causal mutations for about 31% (12\/38) of unrelated individuals with normal chromosomes when compared to about 15% (46\/306) using conventional Sanger sequencing and Multiplex Ligation\u2010dependent Probe Amplification (MLPA). More comprehensive genetic testing by our in house NGS panel sequencing of 10 HPE associated genes (MiSeq\u2122 and NextSeq\u2122500, Illumina, Inc., San Diego, CA) not only allowed to include genes with smaller contribution to the phenotype, but may also unravel additional low frequency or more common genetic variants potentially contributing to the observed large intrafamiliar variability and may ultimately guide our understanding of the individual clinical manifestation of this complex developmental disorder.<\/jats:p>","DOI":"10.1002\/ajmg.c.31625","type":"journal-article","created":{"date-parts":[[2018,7,25]],"date-time":"2018-07-25T04:59:05Z","timestamp":1532494745000},"page":"198-205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre\u2010 and postnatal diagnostic testing in Germany"],"prefix":"10.1002","volume":"178","author":[{"given":"Sophie","family":"Hinreiner","sequence":"first","affiliation":[{"name":"Center for Human Genetics Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Wieczorek","sequence":"additional","affiliation":[{"name":"Medical Faculty, Institute of Human Genetics Heinrich\u2010Heine\u2010University Duesseldorf Duesseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Children's Hospital Chemnitz Chemnitz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Roedl","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundula","family":"Thiel","sequence":"additional","affiliation":[{"name":"Center for Prenatal Diagnosis and Human Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Grasshoff","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University Hospital Tuebingen Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabih","family":"Chaoui","sequence":"additional","affiliation":[{"name":"Center for Prenatal Diagnosis and Human Genetics Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7746-4474","authenticated-orcid":false,"given":"Ute","family":"Hehr","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Regensburg Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1860-1"},{"key":"e_1_2_7_3_1","volume-title":"First trimester ultrasound diagnosis of fetal abnormalities","author":"Abuhamad A.","year":"2017"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-017-0019-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0960-7692.2001.00154.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(82)90025-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.15675"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.202"},{"issue":"3","key":"e_1_2_7_9_1","first-page":"322","article-title":"Diagnosis and management of fetal holoprosencephaly","volume":"66","author":"Chervenak F. 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