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Diagnostic Challenge in PLIN1-Associated Familial Partial Lipodystrophy
- Source :
- Journal of Clinical Endocrinology and Metabolism, Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2019, 104 (12), pp.6025-6032. ⟨10.1210/jc.2019-00849⟩, Journal of Clinical Endocrinology and Metabolism, 2019, 104 (12), pp.6025-6032. ⟨10.1210/jc.2019-00849⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- Context Heterozygous frameshift variants in PLIN1 encoding perilipin-1, a key protein for lipid droplet formation and triglyceride metabolism, have been implicated in familial partial lipodystrophy type 4 (FPLD4), a rare entity with only six families reported worldwide. The pathogenicity of other PLIN1 null variants identified in patients with diabetes and/or hyperinsulinemia was recently questioned because of the absence of lipodystrophy in these individuals and the elevated frequency of PLIN1 null variants in the general population. Objectives To reevaluate the pathogenicity of PLIN1 frameshift variants owing to new data obtained in the largest series of patients with FPLD4. Methods We performed histological and molecular studies for patients referred to our French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity for lipodystrophy and/or insulin resistance and carrying PLIN1 frameshift variants. Results We identified two heterozygous PLIN1 frameshift variants segregating with the phenotype in nine patients from four unrelated families. The FPLD4 stereotypical signs included postpubertal partial lipoatrophy of variable severity, muscular hypertrophy, acromegaloid features, polycystic ovary syndrome and/or hirsutism, metabolic complications (e.g., hypertriglyceridemia, liver steatosis, insulin resistance, diabetes), and disorganized subcutaneous fat lobules with fibrosis and macrophage infiltration. Conclusions These data suggest that some FPLD4-associated PLIN1 variants are deleterious. Thus, the evidence for the pathogenicity of each variant ought to be carefully considered before genetic counseling, especially given the importance of an early diagnosis for optimal disease management. Thus, we recommend detailed familial investigation, adipose tissue-focused examination, and follow-up of metabolic evolution.
- Subjects :
- 0301 basic medicine
Male
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
DNA Mutational Analysis
Case Report
Bioinformatics
Biochemistry
0302 clinical medicine
Endocrinology
Hyperinsulinemia
Frameshift Mutation
ComputingMilieux_MISCELLANEOUS
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
education.field_of_study
Middle Aged
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Polycystic ovary
3. Good health
Lipodystrophy, Familial Partial
Pedigree
Phenotype
Molecular Diagnostic Techniques
Female
Lipodystrophy
Adult
medicine.medical_specialty
Perilipin-1
Population
030209 endocrinology & metabolism
Frameshift mutation
Diagnosis, Differential
03 medical and health sciences
Young Adult
Insulin resistance
Diabetes mellitus
Internal medicine
medicine
Humans
Family
education
Aged
business.industry
Biochemistry (medical)
Sequence Analysis, DNA
medicine.disease
Familial partial lipodystrophy
030104 developmental biology
Insulin Resistance
business
Subjects
Details
- Language :
- English
- ISSN :
- 0021972X and 19457197
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Endocrinology and Metabolism, Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2019, 104 (12), pp.6025-6032. ⟨10.1210/jc.2019-00849⟩, Journal of Clinical Endocrinology and Metabolism, 2019, 104 (12), pp.6025-6032. ⟨10.1210/jc.2019-00849⟩
- Accession number :
- edsair.doi.dedup.....141b43b0bb1bc60cbab50eac296fb450