Furthermore, the newly uncovered compensatory mechanism between DHCR7 and DHCR24 could be of importance for designing medications that would improve cholesterol production in patients with desmosterolosis and Smith-Lemli-Opitz syndrome.
In this study, we assessed the brain content of desmosterol, 7-DHC, and cholesterol from development to adulthood, and analyzed the biochemical, molecular, and anatomical consequences of Dhcr24 mutations on the sterol profile in a mouse model of desmosterolosis and heterozygous Dhcr24<sup>+/-</sup> carriers.
Desmosterolosis is a rare multiple congenital anomaly syndrome caused by a defect in the enzyme 3-beta-hydroxysterol delta-24-reductase (DHCR24) in the cholesterol biosynthesis pathway.
Desmosterolosis is a rare multiple congenital anomaly syndrome caused by a defect in the enzyme 3-beta-hydroxysterol delta-24-reductase (DHCR24) in the cholesterol biosynthesis pathway.
As an example, we measure the relative abundance of the substrate and product sterols of a cholesterol synthetic enzyme, 24-dehydrocholesterol reductase (DHCR24), which is defective in the hereditary developmental disease desmosterolosis.
Desmosterolosis is an autosomal recessive disorder of cholesterol biosynthesis caused by biallelic mutations of DHCR24 (homozygous or compound heterozygous), which encodes 3-β-hydroxysterol Δ-24-reductase.
The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA in yeast.
The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA in yeast.
The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA in yeast.
The diagnosis of desmosterolosis was established by detection of significant elevation of plasma desmosterol levels and reduced enzyme activity of DHCR24 upon expression of the patient's DHCR24 cDNA in yeast.
We describe here the first living patient with desmosterolosis and show biochemical evidence in plasma and cultured lymphoblasts for an autosomal recessive deficiency of 24-dehydrocholesterol reductase (DHCR24).
They impair the activity of a putative C3-sterol dehydrogenase (Nshdl, X-linked dominant bare patches/striated mutation in mice), the sterol delta 8-delta 7 isomerase/EBP (Ebp, X-linked dominant tattered mutation in mice; chondrodysplasia punctata (CDPX2) in humans), the delta 24-sterol reductase (autosomal recessive desmosterolosis) and the delta 7-sterol reductase (DHCR7 gene, autosomal recessive Smith-Lemli-Opitz syndrome in humans).