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URL of this page: https://medlineplus.gov/genetics/gene/bscl2/

BSCL2 gene

BSCL2 lipid droplet biogenesis associated, seipin

Normal Function

The BSCL2 gene provides instructions for making a protein called seipin. Seipin is located in the membrane of a cell structure called the endoplasmic reticulum. The endoplasmic reticulum modifies newly produced proteins and helps transport proteins, fats, and other molecules to where they are needed.

Three different versions (isoforms) of the seipin protein can be produced from the BSCL2 gene. One isoform is found in most tissues, and the other two are specific to the brain and the nervous system outside of the brain.

Studies suggest that seipin plays a critical role in the development and function of adipocytes, which are the major component of fatty (adipose) tissue. Within the endoplasmic reticulum of adipocytes, seipin is involved in the formation of lipid droplets, which are structures that store fat molecules.

Health Conditions Related to Genetic Changes

Congenital generalized lipodystrophy

Variants (also called mutations) in the BSCL2 gene have been identified in people with congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) type 2 . This rare condition is characterized by an almost total absence of adipose tissue and a very muscular appearance. A shortage of adipose tissue leads to multiple health problems, including high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia) and diabetes mellitus, which is a condition in which glucose levels can become dangerously high. In some cases, congenital generalized lipodystrophy type 2 is also associated with mild to moderate intellectual disabilities.

Most of the BSCL2 gene variants that cause congenital generalized lipodystrophy type 2 either prevent cells from making any seipin at all or cause cells to produce a nonfunctional version of this protein. This disrupts the normal function of adipocytes, which prevents fats from being properly stored in adipose tissue. The resulting lack of body fat underlies most of the signs and symptoms of congenital generalized lipodystrophy type 2. A loss of seipin function in the brain may help explain why intellectual disabilities can occur in people with this form of the condition.

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Distal hereditary motor neuropathy, type V

Variants in the BSCL2 gene have been found to cause distal hereditary motor neuropathy, type V. This condition is a disorder that affects the nerve cells that control muscle movement (motor neurons). It results in muscle weakness that impairs the movement of the hands and feet. The variants that cause distal hereditary motor neuropathy, type V change single protein building blocks (amino acids) in the seipin protein, which alters the structure of the protein.

Research indicates that altered seipin proteins build up in the endoplasmic reticulum. This accumulation is thought to damage motor neurons, which leads to muscle weakness and the signs and symptoms of distal hereditary motor neuropathy, type V. The same variant in the BSCL2 gene that causes distal hereditary motor neurtopathy, type V can also cause similar neurological disorders such as Silver syndrome or Charcot-Marie-Tooth disease. People with one of these disorders caused by a BSCL2 gene variant sometimes have family members who have a different condition. While the reason for this is unknown, it is likely that other genetic and environmental influences are involved.

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Silver syndrome

Variants in the BSCL2 gene have been reported to cause Silver syndrome. This condition is characterized by muscle weakness and wasting in the hands and abnormal muscle stiffness (spasticity) in the legs. The variants likely cause cells to produce altered seipin proteins that accumulate within motor neurons, leading to cell damage and cell death. The loss of motor neurons causes muscle weakness and spasticity in people with Silver syndrome.

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Charcot-Marie-Tooth disease

MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease

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Other disorders

A few variants in the BSCL2 gene have been found to cause a very rare condition called progressive encephalopathy with or without lipodystrophy (also known as Celia’s encephalopathy). This condition is characterized by abnormal brain function (encephalopathy) and intellectual disabilities that are apparent early in life. People with this condition may have parts of the body with very little adipose tissue and a very muscular appearance. Individuals with progressive encephalopathy with or without lipodystrophy typically do not survive past childhood.

The BSCL2 gene variants that cause progressive encephalopathy with or without lipodystrophy lead to the deletion of a section of the seipin protein. As a result, the most common isoform that is produced in the brain of affected individuals is not its typical isoform, but the isoform that is usually produced in other tissues. This different isoform forms clumps (aggregates) within neurons. These aggregates damage cells and eventually lead to cell death, causing the severe neurological problems seen in children with progressive encephalopathy with or without lipodystrophy.

Other Names for This Gene

  • Berardinelli-Seip congenital lipodystrophy 2 (seipin)
  • BSCL2_HUMAN
  • GNG3LG
  • seipin
  • SPG17

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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  • Rohkamm B, Reilly MM, Lochmuller H, Schlotter-Weigel B, Barisic N, Schols L, Nicholson G, Pareyson D, Laura M, Janecke AR, Miltenberger-Miltenyi G, John E, Fischer C, Grill F, Wakeling W, Davis M, Pieber TR, Auer-Grumbach M. Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome. J Neurol Sci. 2007 Dec 15;263(1-2):100-6. doi: 10.1016/j.jns.2007.06.047. Epub 2007 Jul 30. Citation on PubMed or Free article on PubMed Central
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