Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant
Abstract
:1. Introduction
2. Experimental Section
2.1. Subjects, Analysis and Interpretation of Variants
2.2. Body Composition Studies
2.3. Biochemical Analyses
2.4. Adipose Tissue Biopsies and Cell Culture
2.5. Adipocyte Differentiation Procedure
2.6. Phase Contrast Microscopy
2.7. RNA Extraction and Retrotranscription
2.8. Real-Time PCR
2.9. Immunofluorescence
2.10. Statistical Analysis
3. Results
3.1. Case Reports
3.2. Cellular and Gene Expression Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Genes | Forward Primer (5′–3′) | Reverse Primer (5′–3′) | Probe | Probe Sequences | Amplicon Length (nt) |
---|---|---|---|---|---|
CEBPA | GCAAATCGTGCCTTGTCAT | CTCATGGGGGTCTGCTGTAG | 12 | CTCCTTCC | 72 |
CEBPB | CGCTTACCTCGGCTACCA | ACGAGGAGGACGTGGAGAG | 74 | CTGCTGCC | 65 |
FABP4 | CCTTTAAAAATACTGAGATTTCCTTCA | GGACACCCCCATCTAAGGTT | 72 | TTCCTGGC | 105 |
GLUT4 | CTGTGCCATCCTGATGACTG | CGTAGCTCATGGCTGGAACT | 67 | TGCTGGAG | 62 |
LPL | ATGTGGCCCGGTTTATCA | CTGTATCCCAAGAGATGGACATT | 25 | CTCCTCCA | 76 |
PPARG | GACCTGAAACTTCAAGAGTACCAAA | TGAGGCTTATTGTAGAGCTGAGTC | 39 | CTCCACCT | 95 |
PREF-1 | GACGGGGAGCTCTGTGATAG | CATAGAGGCCATCGTCCAG | 68 | AGGAGCAG | 94 |
RNA polymerase II | GCATCATGAACAGCGATGAG | TCATCCATCTTGTCCACCAC | 69 | GGAGGAAG | 64 |
Demographic Features | |||||
---|---|---|---|---|---|
Case #1 | Case #2 | Case #3 | Case #4 | Case #5 | |
Age | 42.8 | 53.8 | 34.7 | 18.1 | 62.1 |
Sex | F | F | F | F | F |
Variants | |||||
LMNA | c.1583C>T p.(Thr528Met) | c.1583C>T p.(Thr528Met) | c.1583C>T p.(Thr528Met) | c.1583C>T p.(Thr528Met)/c.1718C>T p.(Ser573Leu) | c.1583C>T p.(Thr528Met) |
Other genes | - | WRN c.1495A>G p.(Arg499Gly); BLM c.813G>C p.(Lys271Asn) | WRN c.1495A>G p.(Arg499Gly); BLM c.813G>C p.(Lys271Asn) | - | - |
Autosomal dominant inheritance | yes | yes | yes | yes | yes |
SNP PPARGp.Pro12Ala | yes | no | no | no | no |
Clinical features | |||||
Acanthosis | no | yes | yes | yes | no |
Phlebomegaly | no | yes | no | yes | yes |
Hypermuscularity | yes | yes | no | no | yes |
Lipomas | no | no | yes | no | no |
Goiter | no | no | no | no | yes |
Diabetes mellitus (DM) | yes | yes | no | no (IFG) | no (IFG) |
Dyslipidemia | IV | IIb | IV | IV | IIb |
Steatosis | no | yes | no | no | no |
Arterial hypertension (AHT) | yes | yes | no | no | yes |
Cardiovascular diseases (CVDs) | no | no | no | no | yes |
Polycystic ovary syndrome (PCOS) and obstetric complications | no | no | no | yes | no |
Pancreatitis | no | no | no | no | no |
Lipodystrophy onset | Childhood | Childhood | 31 years of age | Adolescence | Adolescence |
Family background | Mother and sister: FPLD | Daughter: FPLD; Mother: DM | Mother: FPLD | Father: hypertriglyceridemia | Mother: DM |
Anthropometric data | |||||
Weight (kg) | 58.5 | 73.5 | 58.2 | 61.5 | 60.8 |
Height (cm) | 157 | 159 | 161 | 165 | 160 |
BMI (kg/m2) | 23.7 | 29.1 | 22.5 | 22.6 | 23.8 |
Waist (cm) | 76 | 101 | 84 | 84 | 90 |
Hip (cm) | 87 | 100 | 87 | 94 | 89 |
Waist-to-height ratio | 0.9 | 1 | 1 | 0.9 | 1 |
Waist-to-hip ratio | 0.48 | 0.64 | 0.52 | 0.51 | 0.56 |
Skinfold thickness (mm) | |||||
Triceps | 5.5 | 5 | 16 | 20 | 6 |
Biceps | 4 | 7 | 8 | 11 | 5 |
Suprailiac | 9 | 18 | 23 | 24 | 11 |
Subscapular | 17.5 | 34 | 28 | 52 | 28 |
Thigh | 3.9 | 6 | 15 | 12 | 4 |
Calf | 3.7 | 3 | 15 | 15 | 2 |
DXA scan, fat mass (g) | |||||
Fat % | 21.3 | 31 | 38.6 | 38.9 | 28.9 |
Total fat | 12,442 | 22,800 | 21,680 | 15,720 | 17,569 |
Upper-limb fat | 993 | 2677 | 2757 | 2968 | 1991 |
Lower-limb fat | 2454 | 4735 | 5383 | 6325 | 3151 |
Trunk fat | 8040 | 14,446 | 12,734 | 15,452 | 11,601 |
Visceral fat | 872 | 2070 | 871 | 1023 | 1247 |
Biochemical features | |||||
Basal glucose (mg/dL) | 103 | 218 | 67 | 94 | 96 |
Hemoglobin A1c (%) | 6.2 | 7.2 | 5.3 | 5,.2 | 5.7 |
Plasma insulin (mIU/l) | 5.9 | ND | 20 | 57.8 | 13 |
Peptide C (ng/mL) | ND | 2.1 | ND | 3,4 | 2,2 |
Plasma leptin (ng/mL) | 2.4 | 9.7 | ND | 13 | 3,3 |
Total cholesterol (mg/dL) | 146 | 174 | 264 | 220 | 161 |
Plasma triglycerides (mg/dL) | 372 | 247 | 214 | 338 | 151 |
High-density lipoprotein cholesterol (HDLc) (mg/dL) | 26 | 36 | 53 | 39 | 45 |
Low-density lipoprotein cholesterol (LDLc) (mg/dL) | 39 | 89 | 169 | 113 | 86 |
Alanine aminotransferase (ALT) (IU/L) | 27 | 56 | 13 | 44 | 26 |
Aspartate aminotransferase (AST) (IU/L) | 16 | 65 | 16 | 26 | 20 |
Gamma-glutamyl transpeptidase (GGT) (UI/L) | 9 | 57 | 23 | 23 | 14 |
Creatinine (mg/dL) | 0.81 | 0.5 | 0.5 | 0.59 | 0.64 |
Creatine kinase (CK) | ND | 103 | 54 | 81 | 110 |
Thyroid stimulating hormone (TSH) | 1.43 | 2.02 | 2.78 | 3.27 | 3.58 |
Blood pressure (BP) | 136/79 | 147/80 | 125/69 | 135/89 | 155/87 |
Echocardiogram (ECHO) | - | normal | - | normal | mitral regurgitation |
Medication | Sitagliptin, Fenofibrate, Omega-3 fatty acids, Telmisartan | Metformin, Insulin, Ramipril, Rosuvastatin, Aspirin, Dapaglifozin | - | Metformin | Lormetazepam, Clopidogrel, Aldactone, Atorvastatin |
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Araújo-Vilar, D.; Fernández-Pombo, A.; Victoria, B.; Mosquera-Orgueira, A.; Cobelo-Gómez, S.; Castro-Pais, A.; Hermida-Ameijeiras, Á.; Loidi, L.; Sánchez-Iglesias, S. Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant. J. Clin. Med. 2021, 10, 1497. https://doi.org/10.3390/jcm10071497
Araújo-Vilar D, Fernández-Pombo A, Victoria B, Mosquera-Orgueira A, Cobelo-Gómez S, Castro-Pais A, Hermida-Ameijeiras Á, Loidi L, Sánchez-Iglesias S. Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant. Journal of Clinical Medicine. 2021; 10(7):1497. https://doi.org/10.3390/jcm10071497
Chicago/Turabian StyleAraújo-Vilar, David, Antía Fernández-Pombo, Berta Victoria, Adrián Mosquera-Orgueira, Silvia Cobelo-Gómez, Ana Castro-Pais, Álvaro Hermida-Ameijeiras, Lourdes Loidi, and Sofía Sánchez-Iglesias. 2021. "Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant" Journal of Clinical Medicine 10, no. 7: 1497. https://doi.org/10.3390/jcm10071497
APA StyleAraújo-Vilar, D., Fernández-Pombo, A., Victoria, B., Mosquera-Orgueira, A., Cobelo-Gómez, S., Castro-Pais, A., Hermida-Ameijeiras, Á., Loidi, L., & Sánchez-Iglesias, S. (2021). Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant. Journal of Clinical Medicine, 10(7), 1497. https://doi.org/10.3390/jcm10071497