“Contiguous gene syndrome”的意思、由来-开放百科全书

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. ^¹²{{cite book |title=Human Molecular Genetics | edition = 4th | publisher = Garland Science | pages = 427–428 | last1 = Strachan |first1 = Tom |last2 = Read | first2 = Andrew | location = New York}}
2. ^¹{{cite book |last1=Shaffer |first1=Lisa G.|last2=Ledbetter |first2=David H. |last3=Lupski |first3=James R. |editor1-first=C.W. |editor1-last=Scriver |editor2-first=A.L. |editor2-last=Beaudet |editor3-first=W.S.|editor3-last=Sly |editor4-first=D.|editor4-last=Valle| display-editors = 3 |others= |title=Metabolic and Molecular Bases of Inherited Disease |edition=8th |year=2004 |publisher=McGraw Hill|location=New York |isbn= | pages= |chapter=Molecular Cytogenetics of Contiguous Gene Syndromes: Mechanisms and Consequences of Gene Dosage Imbalance}}