Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy.

CONTEXT: Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare recessive disease characterized by near absence of adipose tissue, resulting in severe dyslipidemia and insulin resistance. In most reported cases, BSCL is due to alterations in either seipin, of unknown function, or 1-acylglycerol-3-phosphate acyltransferase-beta (AGPAT2), which catalyzes the formation of phosphatidic acid. OBJECTIVE: We sought to determine the genetic origin of the unexplained cases of BSCL. We thus sequenced CAV1, encoding caveolin-1, as a candidate gene involved in insulin signaling and lipid homeostasis. CAV1 is a key structural component of plasma membrane caveolae, and Cav1-deficient mice display progressive loss of adipose tissue and insulin resistance. DESIGN: We undertook phenotyping studies and molecular screening of CAV1 in four patients with BSCL with no mutation in the genes encoding either seipin or AGPAT2. RESULTS: A homozygous nonsense mutation (p.Glu38X) was identified in CAV1 in a patient with BSCL born from a consanguineous union. This mutation affects both the alpha- and beta-CAV1 isoforms and ablates CAV1 expression in skin fibroblasts. Detailed magnetic resonance imaging of the proband confirmed near total absence of both sc and visceral adipose tissue, with only vestigial amounts in the dorsal sc regions. In keeping with the lack of adipose tissue, the proband was also severely insulin resistant and dyslipidemic. In addition, the proband had mild hypocalcemia likely due to vitamin D resistance. CONCLUSIONS: These findings identify CAV1 as a new BSCL-related gene and support a critical role for caveolins in human adipocyte function.

Liver adenomatosis: classification of MR imaging features and comparison with pathologic findings.

PURPOSE: To retrospectively compare the clinical manifestation and magnetic resonance (MR) imaging features of liver adenomatosis with pathologic findings. MATERIALS AND METHODS: This study had institutional review board approval, and informed consent was waived. Twenty patients were classified on the basis of pathologic findings into three groups: those with a steatotic, those with a peliotic, and those with a mixed (steatotic and peliotic) form of liver adenomatosis. MR images were reviewed in consensus by two abdominal radiologists, and findings were compared with the pathologic classification. Statistical evaluation was performed with the Student t test. RESULTS: All patients were women (mean age, 39 years +/- 10 [standard deviation]). Lesions of the steatotic form (n = 7) showed (a) a mean diameter of 6.3 cm +/- 1.7, (b) slightly hyperintense signal on T2-weighted images, (c) hyper- or isointense signal on T1-weighted images with a signal dropout with fat suppression sequences, and (d) moderate enhancement at the arterial phase with no delayed enhancement. Lesions of the peliotic form (n = 7) showed (a) a somewhat larger size (8.3 cm +/- 3.6), (b) markedly hyperintense signal on T2-weighted images, (c) iso- or hyperintensity on T1-weighted images with no signal dropout with fat suppression sequences, and (d) strong arterial enhancement and persistent enhancement at the portal and delayed phase. Lesions of the mixed form (n = 6) included a combination of imaging features of the steatotic and peliotic forms. Lesions, however, were significantly larger in the mixed form than in the steatotic form (10.3 cm +/- 4, P < .05). CONCLUSION: There are three patterns of MR imaging features of liver adenomatosis that are associated with three pathologic forms (steatotic, peliotic, and mixed).