Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype?
Abstract Background In the last few years trio‐whole exome sequencing (WES) analysis has demonstrated its potential in obtaining genetic diagnoses even in nonspecific clinical pictures and in atypical presentations of known diseases. Moreover WES allows the detection of variants in multiple genes ca...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-03-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1064 |
| _version_ | 1827345663025741824 |
|---|---|
| author | Lidia Pezzani Laura Pezzoli Alessandra Pansa Barbara Facchinetti Daniela Marchetti Agnese Scatigno Anna R. Lincesso Loredana Perego Monica Pingue Isabella Pellicioli Lucia Migliazza Giovanna Mangili Lorenzo Galletti Ursula Giussani Ezio Bonanomi Anna Cereda Maria Iascone |
| author_facet | Lidia Pezzani Laura Pezzoli Alessandra Pansa Barbara Facchinetti Daniela Marchetti Agnese Scatigno Anna R. Lincesso Loredana Perego Monica Pingue Isabella Pellicioli Lucia Migliazza Giovanna Mangili Lorenzo Galletti Ursula Giussani Ezio Bonanomi Anna Cereda Maria Iascone |
| author_sort | Lidia Pezzani |
| collection | DOAJ |
| description | Abstract Background In the last few years trio‐whole exome sequencing (WES) analysis has demonstrated its potential in obtaining genetic diagnoses even in nonspecific clinical pictures and in atypical presentations of known diseases. Moreover WES allows the detection of variants in multiple genes causing different genetic conditions in a single patient, in about 5% of cases. The resulting phenotype may be clinically discerned as variability in the expression of a known phenotype, or as a new unreported syndromic condition. Methods Trio‐WES was performed on a 4‐month‐old baby with a complex clinical presentation characterized by skeletal anomalies, congenital heart malformation, congenital hypothyroidism, generalized venous and arterial hypoplasia, and recurrent infections. Results WES detected two different homozygous variants, one in CEP57, the gene responsible for mosaic variegated aneuploidy syndrome 2, the other in DYNC2H1, the main gene associated with short‐rib thoracic dysplasia. Conclusion The contribution of these two different genetic causes in determining the phenotype of our patient is discussed, including some clinical signs not explained by the detected variants. The report then highlights the role of WES in providing complete and fast diagnosis in patients with complex presentations of rare genetic syndromes, with important implications in the assessment of recurrence risk. |
| first_indexed | 2024-03-07T23:16:46Z |
| format | Article |
| id | doaj.art-37960e69999c427d889309a579225219 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:46Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-37960e69999c427d889309a5792252192024-02-21T10:43:38ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-03-0183n/an/a10.1002/mgg3.1064Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype?Lidia Pezzani0Laura Pezzoli1Alessandra Pansa2Barbara Facchinetti3Daniela Marchetti4Agnese Scatigno5Anna R. Lincesso6Loredana Perego7Monica Pingue8Isabella Pellicioli9Lucia Migliazza10Giovanna Mangili11Lorenzo Galletti12Ursula Giussani13Ezio Bonanomi14Anna Cereda15Maria Iascone16Laboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyPediatria ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyTerapia Intensiva Pediatrica ASST Papa Giovanni XXIII Bergamo ItalyChirurgia Pediatrica ASST Papa Giovanni XXIII Bergamo ItalyPatologia Neonatale ASST Papa Giovanni XXIII Bergamo ItalyCardiochirurgia ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyTerapia Intensiva Pediatrica ASST Papa Giovanni XXIII Bergamo ItalyPediatria ASST Papa Giovanni XXIII Bergamo ItalyLaboratorio di Genetica Medica ASST Papa Giovanni XXIII Bergamo ItalyAbstract Background In the last few years trio‐whole exome sequencing (WES) analysis has demonstrated its potential in obtaining genetic diagnoses even in nonspecific clinical pictures and in atypical presentations of known diseases. Moreover WES allows the detection of variants in multiple genes causing different genetic conditions in a single patient, in about 5% of cases. The resulting phenotype may be clinically discerned as variability in the expression of a known phenotype, or as a new unreported syndromic condition. Methods Trio‐WES was performed on a 4‐month‐old baby with a complex clinical presentation characterized by skeletal anomalies, congenital heart malformation, congenital hypothyroidism, generalized venous and arterial hypoplasia, and recurrent infections. Results WES detected two different homozygous variants, one in CEP57, the gene responsible for mosaic variegated aneuploidy syndrome 2, the other in DYNC2H1, the main gene associated with short‐rib thoracic dysplasia. Conclusion The contribution of these two different genetic causes in determining the phenotype of our patient is discussed, including some clinical signs not explained by the detected variants. The report then highlights the role of WES in providing complete and fast diagnosis in patients with complex presentations of rare genetic syndromes, with important implications in the assessment of recurrence risk.https://doi.org/10.1002/mgg3.1064CEP57composite phenotypedouble homozygosityDYNC2H1WES |
| spellingShingle | Lidia Pezzani Laura Pezzoli Alessandra Pansa Barbara Facchinetti Daniela Marchetti Agnese Scatigno Anna R. Lincesso Loredana Perego Monica Pingue Isabella Pellicioli Lucia Migliazza Giovanna Mangili Lorenzo Galletti Ursula Giussani Ezio Bonanomi Anna Cereda Maria Iascone Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype? Molecular Genetics & Genomic Medicine CEP57 composite phenotype double homozygosity DYNC2H1 WES |
| title | Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype? |
| title_full | Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype? |
| title_fullStr | Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype? |
| title_full_unstemmed | Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype? |
| title_short | Double homozygosity in CEP57 and DYNC2H1 genes detected by WES: Composite or expanded phenotype? |
| title_sort | double homozygosity in cep57 and dync2h1 genes detected by wes composite or expanded phenotype |
| topic | CEP57 composite phenotype double homozygosity DYNC2H1 WES |
| url | https://doi.org/10.1002/mgg3.1064 |
| work_keys_str_mv | AT lidiapezzani doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT laurapezzoli doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT alessandrapansa doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT barbarafacchinetti doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT danielamarchetti doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT agnesescatigno doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT annarlincesso doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT loredanaperego doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT monicapingue doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT isabellapellicioli doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT luciamigliazza doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT giovannamangili doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT lorenzogalletti doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT ursulagiussani doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT eziobonanomi doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT annacereda doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype AT mariaiascone doublehomozygosityincep57anddync2h1genesdetectedbywescompositeorexpandedphenotype |