Different clinical phenotypes of a pair of siblings with familial hypercholesterolemia: a case report and literature review.

BACKGROUND: Familial hypercholesterolemia (FH) leads to high plasma low-density lipoprotein cholesterol (LDL-C) levels and early cardiovascular morbidity and mortality. We treated a pair of siblings with FH. The cardiovascular manifestations in the proband were more severe than those in his elder sister, although they had almost similar LDL-C levels, ages, and lifestyles. Herein, we report the cases of this family to explore the possible causes of clinical phenotypic differences within the same genetic background. CASE PRESENTATION: We treated a 27-year-old male patient and his 30-year-old sister, both with FH. The coronary angiogram in the male patient revealed 80, 70, and 100% stenosis of the initial, distal right coronary artery branch, and left anterior descending branch, respectively, whereas his sister had almost no coronary stenosis. We treated them accordingly and performed family screening. We found that the LDL-C/particle discordance of the proband is much greater than that of his elder sister. In addition, the average size of LDL-C particle in the proband was smaller than that in his sister. CONCLUSIONS: Patients with FH have a much higher risk of premature atherosclerotic cardiovascular disease, but the clinical manifestations are heterogeneous. The smaller LDL particle size may be the underlying cause for different clinical outcomes in this pair of FH cases and be a potential novel indicator for predicting the prognosis of FH.

Diaryl Ether Formation by a Versatile Thioesterase Domain.

Oxidative coupling and oxidative rearrangement are two of the most common biosynthetic strategies to form diaryl ethers. In contrast, enzymatic diaryl ether generation that proceeds in a nonoxidative manner has not been characterized thus far. Here, we discovered a versatile thioesterase (TE) domain from the nonreducing polyketide synthase (nrPKS) AN7909, which catalyzes diaryl ether formation through a series of successive steps involving esterification, a Smiles rearrangement, and hydrolysis. Further mutations and biochemical analyses with synthetic mimic substrates provide insight into the proposed catalytic process of the TE domain.