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Genetics Home Reference: your guide to understanding genetic conditions
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ISPD

Reviewed August 2013

What is the official name of the ISPD gene?

The official name of this gene is “isoprenoid synthase domain containing.”

ISPD is the gene's official symbol. The ISPD gene is also known by other names, listed below.

What is the normal function of the ISPD gene?

The ISPD gene provides instructions for making a protein that is found in many of the body's tissues but is particularly abundant in the brain.

Although the function of the ISPD protein is unclear, researchers believe that it is involved in the modification of a protein called alpha (α)-dystroglycan. Specifically, ISPD is thought to aid in the addition of chains of sugar molecules to α-dystroglycan through a process known as glycosylation. Glycosylation is critical for the normal function of α-dystroglycan.

The α-dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, glycosylated α-dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.

How are changes in the ISPD gene related to health conditions?

Walker-Warburg syndrome - caused by mutations in the ISPD gene

Mutations in the ISPD gene cause Walker-Warburg syndrome, the most severe form of a group of disorders known as congenital muscular dystrophies. Walker-Warburg syndrome causes muscle weakness and abnormalities of the brain and eyes. Because of the severity of the problems caused by this condition, affected individuals usually do not survive past early childhood.

ISPD gene mutations involved in Walker-Warburg syndrome prevent the normal glycosylation of α-dystroglycan. As a result, α-dystroglycan can no longer effectively anchor cells to the proteins and other molecules that surround them. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, which affects the development, structure, and function of skeletal muscles in people with Walker-Warburg syndrome.

Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead appears bumpy and irregular. Less is known about the effects of ISPD gene mutations on other parts of the body.

other disorders - caused by mutations in the ISPD gene

Mutations in the ISPD gene have been found in individuals with a less severe form of muscular dystrophy known as limb-girdle muscular dystrophy. Individuals with this condition have muscle weakness in the arms and legs that begins in childhood; this weakness leads to difficulty walking. Some people with limb-girdle muscular dystrophy also have heart problems. As in Walker-Warburg syndrome (described above), ISPD gene mutations that cause limb-girdle muscular dystrophy prevent the normal glycosylation of α-dystroglycan. It is unclear how mutations in this gene cause a range of muscular dystrophies.

Where is the ISPD gene located?

Cytogenetic Location: 7p21.2

Molecular Location on chromosome 7: base pairs 16,087,526 to 16,421,321

The ISPD gene is located on the short (p) arm of chromosome 7 at position 21.2.

The ISPD gene is located on the short (p) arm of chromosome 7 at position 21.2.

More precisely, the ISPD gene is located from base pair 16,087,526 to base pair 16,421,321 on chromosome 7.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ISPD?

You and your healthcare professional may find the following resources about ISPD helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ISPD gene or gene products?

  • 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein
  • 4-diphosphocytidyl-2C-methyl-D-erythritol synthase homolog
  • hCG_1745121
  • isoprenoid synthase domain-containing protein
  • IspD
  • ISPD_HUMAN
  • MDDGA7
  • Nip
  • notch1-induced protein

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ISPD?

cell ; congenital ; cytoskeleton ; domain ; extracellular ; extracellular matrix ; gene ; glycosylation ; methyl ; muscle cells ; muscular dystrophy ; neuronal migration ; phosphate ; protein ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Cirak S, Foley AR, Herrmann R, Willer T, Yau S, Stevens E, Torelli S, Brodd L, Kamynina A, Vondracek P, Roper H, Longman C, Korinthenberg R, Marrosu G, Nürnberg P; UK10K Consortium, Michele DE, Plagnol V, Hurles M, Moore SA, Sewry CA, Campbell KP, Voit T, Muntoni F. ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies. Brain. 2013 Jan;136(Pt 1):269-81. doi: 10.1093/brain/aws312. Epub 2013 Jan 3. (http://www.ncbi.nlm.nih.gov/pubmed/23288328?dopt=Abstract)
  • OMIM: ISOPRENOID SYNTHASE DOMAIN-CONTAINING PROTEIN (http://omim.org/entry/614631)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/729920)
  • Roscioli T, Kamsteeg EJ, Buysse K, Maystadt I, van Reeuwijk J, van den Elzen C, van Beusekom E, Riemersma M, Pfundt R, Vissers LE, Schraders M, Altunoglu U, Buckley MF, Brunner HG, Grisart B, Zhou H, Veltman JA, Gilissen C, Mancini GM, Delrée P, Willemsen MA, Ramadža DP, Chitayat D, Bennett C, Sheridan E, Peeters EA, Tan-Sindhunata GM, de Die-Smulders CE, Devriendt K, Kayserili H, El-Hashash OA, Stemple DL, Lefeber DJ, Lin YY, van Bokhoven H. Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. Nat Genet. 2012 May;44(5):581-5. doi: 10.1038/ng.2253. (http://www.ncbi.nlm.nih.gov/pubmed/22522421?dopt=Abstract)
  • Tasca G, Moro F, Aiello C, Cassandrini D, Fiorillo C, Bertini E, Bruno C, Santorelli FM, Ricci E. Limb-girdle muscular dystrophy with α-dystroglycan deficiency and mutations in the ISPD gene. Neurology. 2013 Mar 5;80(10):963-5. doi: 10.1212/WNL.0b013e3182840cbc. Epub 2013 Feb 6. (http://www.ncbi.nlm.nih.gov/pubmed/23390185?dopt=Abstract)
  • Willer T, Lee H, Lommel M, Yoshida-Moriguchi T, de Bernabe DB, Venzke D, Cirak S, Schachter H, Vajsar J, Voit T, Muntoni F, Loder AS, Dobyns WB, Winder TL, Strahl S, Mathews KD, Nelson SF, Moore SA, Campbell KP. ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. Nat Genet. 2012 May;44(5):575-80. doi: 10.1038/ng.2252. (http://www.ncbi.nlm.nih.gov/pubmed/22522420?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2013
Published: October 20, 2014