BSCL2

The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Within cells, seipin is found in the membrane of a tube-like structure called the endoplasmic reticulum. The endoplasmic reticulum modifies newly produced proteins and also helps transport proteins, fats, and other molecules to specific sites either inside or outside the cell. The BSCL2 gene is active in cells throughout the body, particularly nerve cells that control muscle movement (motor neurons) and brain cells. The gene is also active in fat-storing cells called adipocytes, and studies suggest that seipin may play a critical role in the early development of these cells.

Berardinelli-Seip congenital lipodystrophy - caused by mutations in the BSCL2 gene

At least 18 mutations in the BSCL2 gene have been identified in people with Berardinelli-Seip congenital lipodystrophy type 2. Most of these genetic changes lead to the production of a nonfunctional version of the seipin protein. A loss of functional seipin disrupts the normal development and function of adipocytes, which prevents the normal storage of fats in the body. An almost total absence of body fat underlies most of the features of Berardinelli-Seip congenital lipodystrophy.

About 80 percent of people with Berardinelli-Seip congenital lipodystrophy type 2 also have mild to moderate intellectual disability. A loss of the seipin protein in the brain may help explain why cognitive impairment occurs with this condition.

Charcot-Marie-Tooth disease - caused by mutations in the BSCL2 gene

A BSCL2 mutation has been reported in a small number of people with signs and symptoms that are characteristic of Charcot-Marie-Tooth disease type 2. This mutation changes one of the protein building blocks (amino acids) used to make seipin. Specifically, the amino acid asparagine is replaced with the amino acid serine at protein position 88 (written as Asn88Ser or N88S). It is unclear how this mutation causes this disorder. The mutation probably alters the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness in the arms and legs.

distal hereditary motor neuropathy, type V - caused by mutations in the BSCL2 gene

Two BSCL2 mutations have been identified in people with distal hereditary motor neuropathy, type V. These mutations change one of the amino acids used to make seipin. Specifically, the amino acid serine is replaced with the amino leucine at position 90 (written as Ser90Leu or S90L), or the amino acid asparagine is replaced by the amino acid serine at position 88 (written as Asn88Ser or N88S).

It is unclear how BSCL2 mutations cause distal hereditary motor neuropathy, type V. These mutations probably alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness.

other disorders - caused by mutations in the BSCL2 gene

BSCL2 mutations also cause Silver syndrome (sometimes called spastic paraplegia 17), which is characterized by weakness in hand muscles and abnormal muscle stiffness (spasticity) in the legs. These mutations change one of the amino acids in the seipin protein. Specifically, the amino acid asparagine is replaced by the amino acid serine at position 88 (written as Asn88Ser or N88S) or the amino acid serine is replaced with the amino acid leucine at position 90 (written as Ser90Leu or S90L). It is unclear how BSCL2 mutations cause Silver syndrome. These mutations probably alter the structure of seipin, causing it to fold into an incorrect 3-dimensional shape. Research findings indicate that misfolded seipin proteins accumulate in the endoplasmic reticulum. This accumulation likely damages and kills motor neurons, which leads to muscle weakness and spasticity.