{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:08:59Z","timestamp":1790860139280,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Fryns syndrome (FS) is a multiple congenital anomaly syndrome with different multisystemic malformations. These include congenital diaphragmatic hernia, pulmonary hypoplasia, and craniofacial dysmorphic features in combination with malformations of the central nervous system such as agenesis of the corpus callosum, cerebellar hypoplasia, and enlarged ventricles. We present a non-consanguineous northern European family with two recurrent cases of FS: a boy with multiple congenital malformations who died at the age of 2.5 months and a female fetus with a complex developmental disorder with similar features in a following pregnancy. Quad whole exome analysis revealed two likely splicing-affecting disease-causing mutations in the PIGN gene: a synonymous mutation c.2619G&gt;A, p.(Leu873=) in the last nucleotide of exon 29 and a 30 bp-deletion c.996_1023+2del (NM_176787.5) protruding into intron 12, with both mutations in trans configuration in the affected patients. Exon skipping resulting from these two variants was confirmed via RNA sequencing. Our molecular and clinical findings identified compound heterozygosity for two novel splice-affecting variants as the underlying pathomechanism for the development of FS in two patients.<\/jats:p>","DOI":"10.3390\/life14050628","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal Diagnosis of Fryns Syndrome through Identification of Two Novel Splice Variants in the PIGN Gene\u2014A Case Series"],"prefix":"10.3390","volume":"14","author":[{"given":"Aruna","family":"Marchetto","sequence":"first","affiliation":[{"name":"Eurofins Humangenetik und Pr\u00e4natal-Medizin MVZ GmbH, 80639 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Leidescher","sequence":"additional","affiliation":[{"name":"Eurofins Humangenetik und Pr\u00e4natal-Medizin MVZ GmbH, 80639 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresia","family":"van Hoi","sequence":"additional","affiliation":[{"name":"Eurofins Humangenetik und Pr\u00e4natal-Medizin MVZ GmbH, 80639 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Hirschberger","sequence":"additional","affiliation":[{"name":"Eurofins Humangenetik und Pr\u00e4natal-Medizin MVZ GmbH, 80639 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Vogel","sequence":"additional","affiliation":[{"name":"Eurofins Humangenetik und Pr\u00e4natal-Medizin MVZ GmbH, 80639 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegmund","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of Prenatal Medicine and Fetal Therapy, Philipps University, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7688-5357","authenticated-orcid":false,"given":"Ivonne Alexandra","family":"Bedei","sequence":"additional","affiliation":[{"name":"Department of Prenatal Medicine and Fetal Therapy, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Axt-Fliedner","sequence":"additional","affiliation":[{"name":"Department of Prenatal Medicine and Fetal Therapy, Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moneef","family":"Shoukier","sequence":"additional","affiliation":[{"name":"Eurofins Humangenetik und Pr\u00e4natal-Medizin MVZ GmbH, 80639 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-1319","authenticated-orcid":false,"given":"Corinna","family":"Keil","sequence":"additional","affiliation":[{"name":"Department of Prenatal Medicine and Fetal Therapy, Philipps University, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev-biochem-091719-064225","article-title":"RNA Splicing by the Spliceosome","volume":"89","author":"Wilkinson","year":"2020","journal-title":"Annu. 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