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LMNA-associated partial lipodystrophy: anticipation of metabolic complications
- Source :
- Journal of Medical Genetics. 54:413-416
- Publication Year :
- 2017
- Publisher :
- BMJ, 2017.
-
Abstract
- BackgroundType-2 familial partial lipodystrophy (FPLD2) is a rare autosomal dominant lipodystrophic disorder due to mutations inLMNAencoding lamin A/C, a key epigenetic regulator. FPLD2 severity is determined by the occurrence of metabolic complications, especially diabetes and hypertriglyceridaemia. We evaluated the disease history and severity over generations.MethodsThis retrospective study of the largest cohort of patients with FPLD2 reported to date investigates 85 patients from 24 families comprising three generations (G1: n=39; G2: n=41; G3: n=5).ResultsLipodystrophy appears with the same characteristics and at the same age in first generation (G1;18.6±1.5 years) and second generation (G2;15.9±0.8 years). Despite similar body mass index (23.7±0.6 vs 23.8±0.6 kg/m2), the mean delay between the onset of lipodystrophy and diabetes was far shorter in G2 (10.5±2.4 years) than in G1 (29.0±3.5 years) (p=0.0002). The same is true for the delay preceding hypertriglyceridaemia (G2: 4.5±1.4; G1: 19.3±3.2 years) (p=0.002), revealing an anticipation phenomenon. Observations in G3, and analysis within each family of disease history and diagnostic procedures, confirmed this result.ConclusionsThis study is a rare example of anticipation unrelated to a trinucleotide expansion. Discovery of this early occurrence of metabolic complications in young generations underlines the utility of presymptomatic genetic diagnosis, with careful metabolic screening and preventive lifestyle in all at-risk individuals.
- Subjects :
- 0301 basic medicine
Pediatrics
medicine.medical_specialty
business.industry
Partial Lipodystrophy
Retrospective cohort study
Familial partial lipodystrophy
medicine.disease
LMNA
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Endocrinology
Diabetes mellitus
Internal medicine
Anticipation (genetics)
Genetics
medicine
Lipodystrophy
business
Body mass index
030217 neurology & neurosurgery
Genetics (clinical)
Subjects
Details
- ISSN :
- 14686244 and 00222593
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics
- Accession number :
- edsair.doi...........7c73d8fe8893355d92be73d0b15084af