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Normal Function
The NSDHL gene provides instructions for making an enzyme that is involved in the production (synthesis) of cholesterol. Cholesterol is a lipid (fat) that is obtained from foods that come from animals, particularly egg yolks, meat, and dairy products. The body can also make its own cholesterol. During cholesterol synthesis, the NSDHL enzyme participates in one of several steps that convert a molecule called lanosterol to cholesterol. Specifically, the NSDHL enzyme is part of an enzyme complex that removes a carbon atom and three hydrogen atoms (a methyl group) from lanosterol.
Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally. Before birth, cholesterol interacts with signaling proteins that control the early development of the brain, limbs, genital tract, and other structures. It is also an important component of cell membranes and myelin, the fatty covering that insulates nerve cells. Additionally, cholesterol is used to make certain hormones and is important for the production of acids that are used in digestion (bile acids).
Health Conditions Related to Genetic Changes
CHILD syndrome
Several variants (also called mutations) in the NSDHL gene have been found to cause CHILD syndrome, a condition that can affect the development of the arms, legs, and other parts of the body. The signs and symptoms of this disorder are typically limited to only one side of the body.
Most of the variants in the NSDHL gene change single protein building blocks (amino acids) in the NSDHL enzyme. A few other variants delete part or all of the NSDHL gene. Many of these variants prevent the production of any functional NSDHL enzyme, which disrupts the normal synthesis of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol synthesis to build up in the body's tissues. Researchers suspect that low cholesterol levels can contribute to problems with the growth and development of many parts of the body. It is not known, however, exactly how a disturbance in cholesterol synthesis leads to the specific features of CHILD syndrome.
More About This Health ConditionOther Disorders
Variants in the NSDHL gene can cause CK syndrome, a condition characterized by intellectual disabilities and behavior problems in males. Additional symptoms may include seizures, a small head size (microcephaly), and brain abnormalities. Females who have a variant that causes CK syndrome are typically unaffected; however, some may experience mild behavior problems such as irritability or aggression. CK syndrome is very rare; fewer than 30 people with this condition have been reported in the medical literature.
Other Names for This Gene
- H105e3
- NAD(P) dependent steroid dehydrogenase-like
- SDR31E1
- XAP104
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bornholdt D, Konig A, Happle R, Leveleki L, Bittar M, Danarti R, Vahlquist A, Tilgen W, Reinhold U, Poiares Baptista A, Grosshans E, Vabres P, Niiyama S, Sasaoka K, Tanaka T, Meiss AL, Treadwell PA, Lambert D, Camacho F, Grzeschik KH. Mutational spectrum of NSDHL in CHILD syndrome. J Med Genet. 2005 Feb;42(2):e17. doi: 10.1136/jmg.2004.024448. No abstract available. Citation on PubMed or Free article on PubMed Central
- Caldas H, Herman GE. NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets. Hum Mol Genet. 2003 Nov 15;12(22):2981-91. doi: 10.1093/hmg/ddg321. Epub 2003 Sep 23. Citation on PubMed
- Konig A, Happle R, Bornholdt D, Engel H, Grzeschik KH. Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome. Am J Med Genet. 2000 Feb 14;90(4):339-46. Citation on PubMed
- Kurban M, El Feghaly J, Hamie L. NSDHL-Related Disorders. 2011 Feb 1 [updated 2024 Sep 5]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK51754/ Citation on PubMed
- Porter FD, Herman GE. Malformation syndromes caused by disorders of cholesterol synthesis. J Lipid Res. 2011 Jan;52(1):6-34. doi: 10.1194/jlr.R009548. Epub 2010 Oct 7. Citation on PubMed or Free article on PubMed Central
- Porter FD. Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr Opin Pediatr. 2003 Dec;15(6):607-13. doi: 10.1097/00008480-200312000-00011. Citation on PubMed
- Ramphul K, Kota V, Sathe NC, Mejias SG. CHILD Syndrome. 2024 Feb 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK507813/ Citation on PubMed
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