{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T02:12:17Z","timestamp":1769825537179,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Council of Lithuania","award":["S-MIP-21-15"],"award-info":[{"award-number":["S-MIP-21-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Pathogenic variants of PIGN are a known cause of multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). Many affected individuals have clinical features overlapping with Fryns syndrome and are mainly characterised by developmental delay, congenital anomalies, hypotonia, seizures, and specific minor facial anomalies. This study investigates the clinical and molecular data of three individuals from two unrelated families, the clinical features of which were consistent with a diagnosis of MCAHS1. Materials and Methods: Next-generation sequencing (NGS) technology was used to identify the changes in the DNA sequence. Sanger sequencing of gDNA of probands and their parents was used for validation and segregation analysis. Bioinformatics tools were used to investigate the consequences of pathogenic or likely pathogenic PIGN variants at the protein sequence and structure level. Results: The analysis of NGS data and segregation analysis revealed a compound heterozygous NM_176787.5:c.[1942G&gt;T];[1247_1251del] PIGN genotype in family 1 and NG_033144.1(NM_176787.5):c.[932T&gt;G];[1674+1G&gt;C] PIGN genotype in family 2. In silico, c.1942G&gt;T (p.(Glu648Ter)), c.1247_1251del (p.(Glu416GlyfsTer22)), and c.1674+1G&gt;C (p.(Glu525AspfsTer68)) variants are predicted to result in a premature termination codon that leads to truncated and functionally disrupted protein causing the phenotype of MCAHS1 in the affected individuals. Conclusions: PIGN-related disease represents a wide spectrum of phenotypic features, making clinical diagnosis inaccurate and complicated. The genetic testing of every individual with this phenotype provides new insights into the origin and development of the disease.<\/jats:p>","DOI":"10.3390\/medicina58111526","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T07:17:48Z","timestamp":1666768668000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3110-4059","authenticated-orcid":false,"given":"Evelina","family":"Siavrien\u0117","sequence":"first","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017divil\u0117","family":"Mald\u017eien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violeta","family":"Mik\u0161tien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunda","family":"Petraityt\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-6334","authenticated-orcid":false,"given":"Tautvydas","family":"Ran\u010delis","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-6107","authenticated-orcid":false,"given":"Justas","family":"Dapk\u016bnas","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Institute of Biotechnology, Life Sciences Center, Vilnius University, 10257 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birut\u0117","family":"Burnyt\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egl\u0117","family":"Benu\u0161ien\u0117","sequence":"additional","affiliation":[{"name":"Centre for Medical Genetics, Vilnius University Hospital Santaros Klinikos, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Au\u0161ra","family":"Sasnauskien\u0117","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Institute of Biosciences, Life Sciences Centre, Vilnius University, 10257 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurgita","family":"Grikinien\u0117","sequence":"additional","affiliation":[{"name":"Centre of Pediatrics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egl\u0117","family":"Gri\u0161kevi\u010di\u016bt\u0117","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Algirdas","family":"Utkus","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egl\u0117","family":"Preik\u0161aitien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-017-0510-5","article-title":"Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis","volume":"10","author":"Knaus","year":"2018","journal-title":"Genome Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13023-020-01365-0","article-title":"Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS)","volume":"15","author":"Jiao","year":"2020","journal-title":"Orphanet J. 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