Disease relevance of NSDHL

• OBJECTIVE: To analyze the 3beta-hydroxysteroid dehydrogenase (NSDHL) gene in verruciform xanthoma (VX) to elucidate its potential role in the histogenesis of this lesion [1].

High impact information on NSDHL

• In addition to an ER localization commonly found for enzymes of post-squalene cholesterol biosynthesis, we have identified a novel association of NSDHL with lipid droplets, which are endoplasmic reticulum (ER)-derived cytoplasmic structures that contain a neutral lipid core [2].
• The dual localization of NSDHL within ER membranes and on the surface of lipid droplets may provide another mechanism for regulation of the levels and sites of accumulation of intracellular cholesterol [2].
• Analysis of the NSDHL gene showed missense mutation c.370G-->A in these 5 patients [3].
• (2) Known CHILD syndrome mutations in exons 4 and 6 of the NSDHL gene do not contribute to the histogenesis of sporadic VXs [1].
• DESIGN: DNA was extracted from paraffin-embedded tissue, followed by polymerase chain reaction amplification of exons 4 and 6 of the NSDHL gene [1].

Biological context of NSDHL

• We identified a novel missense mutation in NSDHL that potentially may impair protein function [4].
• Recently, we elucidated the underlying gene defect by demonstrating point mutations in NSDHL (NAD[P]H steroid dehydrogenase-like protein) at Xq28 in 6 patients with classic CHILD syndrome [4].
• Apparently, the effect of random X-inactivation is responsible for different patterns of cutaneous involvement in female carriers of NSDHL mutations [4].
• The phenotype was shown to be associated with a deletion of exons 6-8 of the X-linked NSDHL gene, confirming that CHILD syndrome is due to loss of function of an enzyme involved in cholesterol biosynthesis [5].

Associations of NSDHL with chemical compounds

• Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome [6].
• NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets [2].

Analytical, diagnostic and therapeutic context of NSDHL

• SSCA and genomic sequence analysis of NSDHL identified in 6 patients with CHILD syndrome, including one boy as well as a mother and her daughter, mutations potentially impairing protein function [6].

References