Missing in action: the genetic mysteries of extremely low HDL cholesterol
IntroductionHigh-Density Lipoprotein Cholesterol (HDL-C) plays a pivotal role in cardiovascular health, acting as a key component in lipid transport and atheroprotection. While low HDL-C levels in the general population are often the result of multifactorial causes, extremely low HDL-C levels (&...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1553259/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850260621965131776 |
|---|---|
| author | Shoshi Sphitzen Mordechai Golomb Mohammad Mowaswes Refael Bitzur Smadar Horowitz Cederboim Ronen R. Leker Marc Gotkine Itai Chovers Daniel Schurr Eran Leitersdorf Ronen Durst Ronen Durst |
| author_facet | Shoshi Sphitzen Mordechai Golomb Mohammad Mowaswes Refael Bitzur Smadar Horowitz Cederboim Ronen R. Leker Marc Gotkine Itai Chovers Daniel Schurr Eran Leitersdorf Ronen Durst Ronen Durst |
| author_sort | Shoshi Sphitzen |
| collection | DOAJ |
| description | IntroductionHigh-Density Lipoprotein Cholesterol (HDL-C) plays a pivotal role in cardiovascular health, acting as a key component in lipid transport and atheroprotection. While low HDL-C levels in the general population are often the result of multifactorial causes, extremely low HDL-C levels (<20 mg/dl) are rare and may be attributed to underlying genetic defects. Mutations in genes such as LCAT, APOA1, and ABCA1—although exceedingly rare—have been linked to profound alterations in lipid metabolism, often resulting in significant morbidity and increased cardiovascular risk.MethodsIn this study, we used exome sequencing on patients with very low HDL-C.ResultsWe identified three patients with pathogenic mutations associated with genetic low HDL-C syndrome, including ABCA1 [NM_005502.4(ABCA1):c.4175 + 1G > T, chr:9 91757308° C > A, rs375247413], LCAT [NM_000229.2(LCAT):c.349G > A p.Ala117Thr, rs28940886], and APOA1 [NM_000039.3(APOA1):c.388A > T, p.Lys130*].DiscussionEach case presented a unique spectrum of clinical phenotypes, systemic complications, and biochemical abnormalities, illustrating the diverse impact of these genetic mutations. We provide a detailed analysis of the clinical and biochemical profiles of these patients, highlighting key aspects of disease manifestation and progression. This report underscores the importance of recognizing and characterizing rare genetic causes of low HDL-C, which may have profound implications for patient care and risk stratification. |
| format | Article |
| id | doaj-art-3fd8516f1f1443ce8130490847e05a76 |
| institution | OA Journals |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-3fd8516f1f1443ce8130490847e05a762025-08-20T01:55:37ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-05-011210.3389/fcvm.2025.15532591553259Missing in action: the genetic mysteries of extremely low HDL cholesterolShoshi Sphitzen0Mordechai Golomb1Mohammad Mowaswes2Refael Bitzur3Smadar Horowitz Cederboim4Ronen R. Leker5Marc Gotkine6Itai Chovers7Daniel Schurr8Eran Leitersdorf9Ronen Durst10Ronen Durst11Lipid Clinic and Center for Cardiovascular Precision Medicine, Hadassah Hebrew University Medical Center, Jerusalem, IsraelCardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, IsraelCardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, IsraelThe Bert W. Strassburger Lipid Center, Sheba Medical Center, Ramat Gan, IsraelLipid Clinic and Center for Cardiovascular Precision Medicine, Hadassah Hebrew University Medical Center, Jerusalem, IsraelDepartment of Neurology, Hadassah Hebrew University Medical Center, Jerusalem, IsraelDepartment of Neurology, Hadassah Hebrew University Medical Center, Jerusalem, IsraelOphthalmology Department, Hadassah Hebrew University Medical Center, Jerusalem, IsraelLipid Clinic and Center for Cardiovascular Precision Medicine, Hadassah Hebrew University Medical Center, Jerusalem, IsraelLipid Clinic and Center for Cardiovascular Precision Medicine, Hadassah Hebrew University Medical Center, Jerusalem, IsraelLipid Clinic and Center for Cardiovascular Precision Medicine, Hadassah Hebrew University Medical Center, Jerusalem, IsraelCardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, IsraelIntroductionHigh-Density Lipoprotein Cholesterol (HDL-C) plays a pivotal role in cardiovascular health, acting as a key component in lipid transport and atheroprotection. While low HDL-C levels in the general population are often the result of multifactorial causes, extremely low HDL-C levels (<20 mg/dl) are rare and may be attributed to underlying genetic defects. Mutations in genes such as LCAT, APOA1, and ABCA1—although exceedingly rare—have been linked to profound alterations in lipid metabolism, often resulting in significant morbidity and increased cardiovascular risk.MethodsIn this study, we used exome sequencing on patients with very low HDL-C.ResultsWe identified three patients with pathogenic mutations associated with genetic low HDL-C syndrome, including ABCA1 [NM_005502.4(ABCA1):c.4175 + 1G > T, chr:9 91757308° C > A, rs375247413], LCAT [NM_000229.2(LCAT):c.349G > A p.Ala117Thr, rs28940886], and APOA1 [NM_000039.3(APOA1):c.388A > T, p.Lys130*].DiscussionEach case presented a unique spectrum of clinical phenotypes, systemic complications, and biochemical abnormalities, illustrating the diverse impact of these genetic mutations. We provide a detailed analysis of the clinical and biochemical profiles of these patients, highlighting key aspects of disease manifestation and progression. This report underscores the importance of recognizing and characterizing rare genetic causes of low HDL-C, which may have profound implications for patient care and risk stratification.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1553259/fullHDL-CtangiesLCATABCA1apoA1 |
| spellingShingle | Shoshi Sphitzen Mordechai Golomb Mohammad Mowaswes Refael Bitzur Smadar Horowitz Cederboim Ronen R. Leker Marc Gotkine Itai Chovers Daniel Schurr Eran Leitersdorf Ronen Durst Ronen Durst Missing in action: the genetic mysteries of extremely low HDL cholesterol Frontiers in Cardiovascular Medicine HDL-C tangies LCAT ABCA1 apoA1 |
| title | Missing in action: the genetic mysteries of extremely low HDL cholesterol |
| title_full | Missing in action: the genetic mysteries of extremely low HDL cholesterol |
| title_fullStr | Missing in action: the genetic mysteries of extremely low HDL cholesterol |
| title_full_unstemmed | Missing in action: the genetic mysteries of extremely low HDL cholesterol |
| title_short | Missing in action: the genetic mysteries of extremely low HDL cholesterol |
| title_sort | missing in action the genetic mysteries of extremely low hdl cholesterol |
| topic | HDL-C tangies LCAT ABCA1 apoA1 |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1553259/full |
| work_keys_str_mv | AT shoshisphitzen missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT mordechaigolomb missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT mohammadmowaswes missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT refaelbitzur missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT smadarhorowitzcederboim missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT ronenrleker missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT marcgotkine missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT itaichovers missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT danielschurr missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT eranleitersdorf missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT ronendurst missinginactionthegeneticmysteriesofextremelylowhdlcholesterol AT ronendurst missinginactionthegeneticmysteriesofextremelylowhdlcholesterol |