1/2. A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2.CONTEXT: To date, all cases of familial partial lipodystrophy type 2 (FPLD2; Mendelian Inheritance in Man 151660) result from missense mutations in LMNA, which encodes nuclear lamin A/C (Mendelian Inheritance in Man 150330). OBJECTIVE: The objective of the study was to carry out mutational analysis of LMNA in two sisters with a particularly severe FPLD2 phenotype. DESIGN: This was a descriptive case report with molecular studies. SETTING: The study was conducted at a referral center. patients: We report two sisters of South Asian origin. The first presented with acanthosis nigricans at age 5 yr, diabetes with insulin resistance, hypertension and hypertriglyceridemia at age 13 yr, and partial lipodystrophy starting at puberty. Her sister and their mother had a similar metabolic profile and physical features, and their mother died of vascular disease at age 32 yr. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES AND RESULTS: LMNA sequencing showed that the sisters were each heterozygous for a novel G>C mutation at the intron 8 consensus splice donor site, which was absent from the genomes of 300 healthy individuals. The retention of intron 8 in mRNA predicted a prematurely truncated lamin A isoform (516 instead of 664 amino acids) with 20 nonsense 3'-terminal residues. The mutant lamin A isoform failed to interact normally with emerin and failed to localize to the nuclear envelope. CONCLUSIONS: This is the first LMNA splicing mutation to be associated with FPLD2, and it causes a severe clinical and metabolic phenotype.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/2. A 47-year-old man with eruptions on his trunk.A 47-year-old white male came to the hospital emergency department complaining of chest pain. At admission, it was noted that the patient had numerous lesions on his buttocks, abdomen, back, and all extremities. These lesions had been there for approximately 5 months--they developed after he discontinued his cholesterol medication due to lapsed insurance coverage. He had a similar eruption when he went off cholesterol medication on another occasion. The patient's medical history included type 2 diabetes mellitus, hypertension, coronary artery disease, and hyperlipidemia. He has had multiple heart catheterizations with stent placement, most recently 2 years ago. His mother also had diabetes mellitus, and she died at age 58 from a myocardial infarction. On examination, his lesions were painless and nonpruritic. He had numerous yellow papules on his buttocks, abdomen, back, and upper and lower extremities. He had no lesions on his face. The rest of the physical exam showed no abnormal results. What is your diagnosis? What laboratory tests should be done to help make the diagnosis?- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |