Contiguous gene syndrome

A contiguous gene syndrome (CGS), also known as a contiguous gene deletion syndrome, is a clinical phenotype caused by a chromosomal abnormality, such as a deletion or duplication that removes several genes lying in close proximity to one another on the chromosome. The combined phenotype of the patient is a combination of what is seen when any individual has disease-causing mutations in any of the individual genes involved in the deletion. While it can be caused by deleted material on a chromosome, it is not, strictly speaking, the same entity as a segmental aneuploidy syndrome. A segmental aneuploidy syndrome is a subtype of CGS that regularly recur, usually due to non-allelic homologous recombination between low copy repeats in the region.^[1] Most CGS involve the X chromosome and affect male individuals.^[2]

One of the earliest and most famous examples of a CGS involves a male patient with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CGD), retinitis pigmentosa and intellectual disability. When it was discovered that an X chromosome deletion (specifically Xp21) was the underlying cause of all of these features, researchers were able to use this information to clone the genes responsible for DMD and CGD.^[1]

One of those more common CGS involves a deletion on the X chromosome (near Xp21) that encompasses DMD (causing Duchenne muscular dystrophy), NROB1 (causing X-linked adrenal hypoplasia congenita) and GK (causing glycerol kinase deficiency). These patients will have all the common features of each individual disease, resulting in a very complex phenotype.^[2] Deletions near the distal tip of the p arm of the X chromosome are also a frequent cause of CGS. In addition to the previously described CGS that occur on the X chromosome, two other common syndromes are Langer–Giedion syndrome (caused by deletions of TRPS1 and EXT1 on 8q24 and WAGR syndrome (caused by deletions on 11q13 encompassing PAX6 and WT1.)^[1]

References

1. Strachan, Tom; Read, Andrew. Human Molecular Genetics (4th ed.). New York: Garland Science. pp. 427–428.
2. Shaffer, Lisa G.; Ledbetter, David H.; Lupski, James R. (2004). "Molecular Cytogenetics of Contiguous Gene Syndromes: Mechanisms and Consequences of Gene Dosage Imbalance". In Scriver, C.W.; Beaudet, A.L.; Sly, W.S.; et al. (eds.). Metabolic and Molecular Bases of Inherited Disease (8th ed.). New York: McGraw Hill.