A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia
Background: Hypertriglyceridemia (HTG) is one of the most common forms of lipid metabolism disorders. The leading clinical manifestations are pancreatitis, atherosclerotic vascular lesions, and the formation of eruptive xanthomas. The most severe type of HTG is primary (or hereditary) hypertriglycer...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/6/1062 |
| _version_ | 1797487084531875840 |
|---|---|
| author | Petr Andreevich Vasiluev Olga N. Ivanova Natalia A. Semenova Tatiana V. Strokova Natalia N. Taran Uliana V. Chubykina Marat V. Ezhov Ekaterina Y. Zakharova Elena L. Dadli Sergey I. Kutsev |
| author_facet | Petr Andreevich Vasiluev Olga N. Ivanova Natalia A. Semenova Tatiana V. Strokova Natalia N. Taran Uliana V. Chubykina Marat V. Ezhov Ekaterina Y. Zakharova Elena L. Dadli Sergey I. Kutsev |
| author_sort | Petr Andreevich Vasiluev |
| collection | DOAJ |
| description | Background: Hypertriglyceridemia (HTG) is one of the most common forms of lipid metabolism disorders. The leading clinical manifestations are pancreatitis, atherosclerotic vascular lesions, and the formation of eruptive xanthomas. The most severe type of HTG is primary (or hereditary) hypertriglyceridemia, linked to pathogenic genetic variants in <i>LPL</i>, <i>APOC2</i>, <i>LMF1,</i> and <i>APOA5</i> genes. Case: We present a clinical case of severe primary hypertriglyceridemia (TG level > 55 mmol/L in a 4-year-old boy) in a consanguineous family. The disease developed due to a previously undescribed homozygous deletion in the <i>APOA5</i> gene (NM_052968: c.579_592delATACGCCGAGAGCC p.Tyr194Gly*68). We also evaluate the clinical significance of a genetic variant in the <i>LPL</i> gene (NM_000237.2: c.106G>A (rs1801177) p.Asp36Asn), which was previously described as a polymorphism. In one family, we also present a different clinical significance even in heterozygous carriers: from hypertriglyceridemia to normotriglyceridemia. We provide evidence that this heterogeneity has developed due to polymorphism in the <i>LPL</i> gene, which plays the role of an additional trigger. Conclusions: The homozygous deletion of the <i>APOA5</i> gene is responsible for the severe hypertriglyceridemia, and another SNP in the <i>LPL</i> gene worsens the course of the disease. |
| first_indexed | 2024-03-09T23:42:49Z |
| format | Article |
| id | doaj.art-56281b69b8ac4efabaaeeec999980dfc |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T23:42:49Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-56281b69b8ac4efabaaeeec999980dfc2023-11-23T16:48:38ZengMDPI AGGenes2073-44252022-06-01136106210.3390/genes13061062A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe HypertriglyceridemiaPetr Andreevich Vasiluev0Olga N. Ivanova1Natalia A. Semenova2Tatiana V. Strokova3Natalia N. Taran4Uliana V. Chubykina5Marat V. Ezhov6Ekaterina Y. Zakharova7Elena L. Dadli8Sergey I. Kutsev9Research Centre for Medical Genetics, Moskvorechye Street, 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye Street, 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye Street, 1, 115522 Moscow, RussiaFederal Research Centre of Nutrition and Biotechnology, Kashirskoe Shosse, d. 21, 115446 Moscow, RussiaFederal Research Centre of Nutrition and Biotechnology, Kashirskoe Shosse, d. 21, 115446 Moscow, RussiaFederal State Budget Organization «Chazov National Medical Research Center of Cardiology» of the Ministry of Health of the Russian Federation, 3rd Cherepkovskaya Street 15a, 121552 Moscow, RussiaFederal State Budget Organization «Chazov National Medical Research Center of Cardiology» of the Ministry of Health of the Russian Federation, 3rd Cherepkovskaya Street 15a, 121552 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye Street, 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye Street, 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye Street, 1, 115522 Moscow, RussiaBackground: Hypertriglyceridemia (HTG) is one of the most common forms of lipid metabolism disorders. The leading clinical manifestations are pancreatitis, atherosclerotic vascular lesions, and the formation of eruptive xanthomas. The most severe type of HTG is primary (or hereditary) hypertriglyceridemia, linked to pathogenic genetic variants in <i>LPL</i>, <i>APOC2</i>, <i>LMF1,</i> and <i>APOA5</i> genes. Case: We present a clinical case of severe primary hypertriglyceridemia (TG level > 55 mmol/L in a 4-year-old boy) in a consanguineous family. The disease developed due to a previously undescribed homozygous deletion in the <i>APOA5</i> gene (NM_052968: c.579_592delATACGCCGAGAGCC p.Tyr194Gly*68). We also evaluate the clinical significance of a genetic variant in the <i>LPL</i> gene (NM_000237.2: c.106G>A (rs1801177) p.Asp36Asn), which was previously described as a polymorphism. In one family, we also present a different clinical significance even in heterozygous carriers: from hypertriglyceridemia to normotriglyceridemia. We provide evidence that this heterogeneity has developed due to polymorphism in the <i>LPL</i> gene, which plays the role of an additional trigger. Conclusions: The homozygous deletion of the <i>APOA5</i> gene is responsible for the severe hypertriglyceridemia, and another SNP in the <i>LPL</i> gene worsens the course of the disease.https://www.mdpi.com/2073-4425/13/6/1062hypertriglyceridemiapancreatitiscardiovascular disease<i>APOA5</i><i>LPL</i>mutation |
| spellingShingle | Petr Andreevich Vasiluev Olga N. Ivanova Natalia A. Semenova Tatiana V. Strokova Natalia N. Taran Uliana V. Chubykina Marat V. Ezhov Ekaterina Y. Zakharova Elena L. Dadli Sergey I. Kutsev A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia Genes hypertriglyceridemia pancreatitis cardiovascular disease <i>APOA5</i> <i>LPL</i> mutation |
| title | A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia |
| title_full | A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia |
| title_fullStr | A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia |
| title_full_unstemmed | A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia |
| title_short | A Clinical Case of a Homozygous Deletion in the <i>APOA5</i> Gene with Severe Hypertriglyceridemia |
| title_sort | clinical case of a homozygous deletion in the i apoa5 i gene with severe hypertriglyceridemia |
| topic | hypertriglyceridemia pancreatitis cardiovascular disease <i>APOA5</i> <i>LPL</i> mutation |
| url | https://www.mdpi.com/2073-4425/13/6/1062 |
| work_keys_str_mv | AT petrandreevichvasiluev aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT olganivanova aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT nataliaasemenova aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT tatianavstrokova aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT nataliantaran aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT ulianavchubykina aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT maratvezhov aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT ekaterinayzakharova aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT elenaldadli aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT sergeyikutsev aclinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT petrandreevichvasiluev clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT olganivanova clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT nataliaasemenova clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT tatianavstrokova clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT nataliantaran clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT ulianavchubykina clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT maratvezhov clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT ekaterinayzakharova clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT elenaldadli clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia AT sergeyikutsev clinicalcaseofahomozygousdeletionintheiapoa5igenewithseverehypertriglyceridemia |