PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation
<i>Background and Objectives</i>: Pathogenic variants of <i>PIGN</i> 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 dev...
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MDPI AG
2022-10-01
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| author | Evelina Siavrienė Živilė Maldžienė Violeta Mikštienė Gunda Petraitytė Tautvydas Rančelis Justas Dapkūnas Birutė Burnytė Eglė Benušienė Aušra Sasnauskienė Jurgita Grikinienė Eglė Griškevičiūtė Algirdas Utkus Eglė Preikšaitienė |
| author_facet | Evelina Siavrienė Živilė Maldžienė Violeta Mikštienė Gunda Petraitytė Tautvydas Rančelis Justas Dapkūnas Birutė Burnytė Eglė Benušienė Aušra Sasnauskienė Jurgita Grikinienė Eglė Griškevičiūtė Algirdas Utkus Eglė Preikšaitienė |
| author_sort | Evelina Siavrienė |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Pathogenic variants of <i>PIGN</i> 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. <i>Materials and Methods</i>: 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 <i>PIGN</i> variants at the protein sequence and structure level. <i>Results</i>: The analysis of NGS data and segregation analysis revealed a compound heterozygous NM_176787.5:c.[1942G>T];[1247_1251del] <i>PIGN</i> genotype in family 1 and NG_033144.1(NM_176787.5):c.[932T>G];[1674+1G>C] <i>PIGN</i> genotype in family 2. In silico, c.1942G>T (p.(Glu648Ter)), c.1247_1251del (p.(Glu416GlyfsTer22)), and c.1674+1G>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. <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-09T18:51:31Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T18:51:31Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
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| series | Medicina |
| spelling | doaj.art-0d4f223e52f746da93d29b17009c60142023-11-24T05:46:17ZengMDPI AGMedicina1010-660X1648-91442022-10-015811152610.3390/medicina58111526PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical CharacterisationEvelina Siavrienė0Živilė Maldžienė1Violeta Mikštienė2Gunda Petraitytė3Tautvydas Rančelis4Justas Dapkūnas5Birutė Burnytė6Eglė Benušienė7Aušra Sasnauskienė8Jurgita Grikinienė9Eglė Griškevičiūtė10Algirdas Utkus11Eglė Preikšaitienė12Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaDepartment of Bioinformatics, Institute of Biotechnology, Life Sciences Center, Vilnius University, 10257 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaCentre for Medical Genetics, Vilnius University Hospital Santaros Klinikos, 08410 Vilnius, LithuaniaDepartment of Biochemistry and Molecular Biology, Institute of Biosciences, Life Sciences Centre, Vilnius University, 10257 Vilnius, LithuaniaCentre of Pediatrics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 03101 Vilnius, LithuaniaFaculty of Medicine, Vilnius University, 03101 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, LithuaniaDepartment of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 08410 Vilnius, Lithuania<i>Background and Objectives</i>: Pathogenic variants of <i>PIGN</i> 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. <i>Materials and Methods</i>: 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 <i>PIGN</i> variants at the protein sequence and structure level. <i>Results</i>: The analysis of NGS data and segregation analysis revealed a compound heterozygous NM_176787.5:c.[1942G>T];[1247_1251del] <i>PIGN</i> genotype in family 1 and NG_033144.1(NM_176787.5):c.[932T>G];[1674+1G>C] <i>PIGN</i> genotype in family 2. In silico, c.1942G>T (p.(Glu648Ter)), c.1247_1251del (p.(Glu416GlyfsTer22)), and c.1674+1G>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. <i>Conclusions</i>: 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.https://www.mdpi.com/1648-9144/58/11/1526<i>PIGN</i>compound heterogeneous variantsmultiple congenital anomalies-hypotonia-seizures syndrome 1Fryns syndromecongenital anomalies |
| spellingShingle | Evelina Siavrienė Živilė Maldžienė Violeta Mikštienė Gunda Petraitytė Tautvydas Rančelis Justas Dapkūnas Birutė Burnytė Eglė Benušienė Aušra Sasnauskienė Jurgita Grikinienė Eglė Griškevičiūtė Algirdas Utkus Eglė Preikšaitienė PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation Medicina <i>PIGN</i> compound heterogeneous variants multiple congenital anomalies-hypotonia-seizures syndrome 1 Fryns syndrome congenital anomalies |
| title | PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation |
| title_full | PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation |
| title_fullStr | PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation |
| title_full_unstemmed | PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation |
| title_short | PIGN-Related Disease in Two Lithuanian Families: A Report of Two Novel Pathogenic Variants, Molecular and Clinical Characterisation |
| title_sort | pign related disease in two lithuanian families a report of two novel pathogenic variants molecular and clinical characterisation |
| topic | <i>PIGN</i> compound heterogeneous variants multiple congenital anomalies-hypotonia-seizures syndrome 1 Fryns syndrome congenital anomalies |
| url | https://www.mdpi.com/1648-9144/58/11/1526 |
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