Novel findings from family-based exome sequencing for children with biliary atresia
Abstract Biliary atresia (BA) is a progressive inflammation and fibrosis of the biliary tree characterized by the obstruction of bile flow, which results in liver failure, scarring and cirrhosis. This study aimed to explore the elusive aetiology of BA by conducting whole exome sequencing for 41 chil...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-01148-y |
| _version_ | 1819045511473135616 |
|---|---|
| author | Kien Trung Tran Vinh Sy Le Lan Thi Mai Dao Huyen Khanh Nguyen Anh Kieu Mai Ha Thi Nguyen Minh Duy Ngo Quynh Anh Tran Liem Thanh Nguyen |
| author_facet | Kien Trung Tran Vinh Sy Le Lan Thi Mai Dao Huyen Khanh Nguyen Anh Kieu Mai Ha Thi Nguyen Minh Duy Ngo Quynh Anh Tran Liem Thanh Nguyen |
| author_sort | Kien Trung Tran |
| collection | DOAJ |
| description | Abstract Biliary atresia (BA) is a progressive inflammation and fibrosis of the biliary tree characterized by the obstruction of bile flow, which results in liver failure, scarring and cirrhosis. This study aimed to explore the elusive aetiology of BA by conducting whole exome sequencing for 41 children with BA and their parents (35 trios, including 1 family with 2 BA-diagnosed children and 5 child-mother cases). We exclusively identified and validated a total of 28 variants (17 X-linked, 6 de novo and 5 homozygous) in 25 candidate genes from our BA cohort. These variants were among the 10% most deleterious and had a low minor allele frequency against the employed databases: Kinh Vietnamese (KHV), GnomAD and 1000 Genome Project. Interestingly, AMER1, INVS and OCRL variants were found in unrelated probands and were first reported in a BA cohort. Liver specimens and blood samples showed identical variants, suggesting that somatic variants were unlikely to occur during morphogenesis. Consistent with earlier attempts, this study implicated genetic heterogeneity and non-Mendelian inheritance of BA. |
| first_indexed | 2024-12-21T10:29:44Z |
| format | Article |
| id | doaj.art-d0600d62a85a424a938255c883bbfd6e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T10:29:44Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d0600d62a85a424a938255c883bbfd6e2022-12-21T19:07:13ZengNature PortfolioScientific Reports2045-23222021-11-0111111310.1038/s41598-021-01148-yNovel findings from family-based exome sequencing for children with biliary atresiaKien Trung Tran0Vinh Sy Le1Lan Thi Mai Dao2Huyen Khanh Nguyen3Anh Kieu Mai4Ha Thi Nguyen5Minh Duy Ngo6Quynh Anh Tran7Liem Thanh Nguyen8Vinmec Research Institute of Stem Cell and Gene TechnologyVinmec Research Institute of Stem Cell and Gene TechnologyVinmec Research Institute of Stem Cell and Gene TechnologyBioequivalence Center, National Institute of Drug Quality ControlVinmec International HospitalVinmec International HospitalVinmec International HospitalVietnam National Children’s HospitalVinmec Research Institute of Stem Cell and Gene TechnologyAbstract Biliary atresia (BA) is a progressive inflammation and fibrosis of the biliary tree characterized by the obstruction of bile flow, which results in liver failure, scarring and cirrhosis. This study aimed to explore the elusive aetiology of BA by conducting whole exome sequencing for 41 children with BA and their parents (35 trios, including 1 family with 2 BA-diagnosed children and 5 child-mother cases). We exclusively identified and validated a total of 28 variants (17 X-linked, 6 de novo and 5 homozygous) in 25 candidate genes from our BA cohort. These variants were among the 10% most deleterious and had a low minor allele frequency against the employed databases: Kinh Vietnamese (KHV), GnomAD and 1000 Genome Project. Interestingly, AMER1, INVS and OCRL variants were found in unrelated probands and were first reported in a BA cohort. Liver specimens and blood samples showed identical variants, suggesting that somatic variants were unlikely to occur during morphogenesis. Consistent with earlier attempts, this study implicated genetic heterogeneity and non-Mendelian inheritance of BA.https://doi.org/10.1038/s41598-021-01148-y |
| spellingShingle | Kien Trung Tran Vinh Sy Le Lan Thi Mai Dao Huyen Khanh Nguyen Anh Kieu Mai Ha Thi Nguyen Minh Duy Ngo Quynh Anh Tran Liem Thanh Nguyen Novel findings from family-based exome sequencing for children with biliary atresia Scientific Reports |
| title | Novel findings from family-based exome sequencing for children with biliary atresia |
| title_full | Novel findings from family-based exome sequencing for children with biliary atresia |
| title_fullStr | Novel findings from family-based exome sequencing for children with biliary atresia |
| title_full_unstemmed | Novel findings from family-based exome sequencing for children with biliary atresia |
| title_short | Novel findings from family-based exome sequencing for children with biliary atresia |
| title_sort | novel findings from family based exome sequencing for children with biliary atresia |
| url | https://doi.org/10.1038/s41598-021-01148-y |
| work_keys_str_mv | AT kientrungtran novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT vinhsyle novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT lanthimaidao novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT huyenkhanhnguyen novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT anhkieumai novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT hathinguyen novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT minhduyngo novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT quynhanhtran novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia AT liemthanhnguyen novelfindingsfromfamilybasedexomesequencingforchildrenwithbiliaryatresia |