A contiguous gene syndrome (CGS), also known as a contiguous gene deletion syndrome, is a clinical

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

caused by a

chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

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 Non-allelic homologous recombination (NAHR) is a form of homologous recombination that occurs between two lengths of DNA that have high sequence similarity, but are not alleles. It usually occurs between sequences of DNA that have been previously ...

between low copy repeats in the region. Most CGS involve the

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...

and affect male individuals. One of the earliest and most famous examples of a CGS involves a male patient with

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis fol ...

(DMD),

chronic granulomatous disease Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reacti ...

(CGD),

retinitis pigmentosa Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...

and

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

. 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. 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 X-linked adrenal hypoplasia congenita is a genetic disorder that mainly affects males. It involves many endocrine tissues in the body, especially the adrenal glands. Presentation One of the main characteristics of this disorder is adrenal insuffic ...

) and '' GK'' (causing

glycerol kinase deficiency Glycerol kinase deficiency (GKD) is an X-linked recessive enzyme defect that is heterozygous in nature. Three clinically distinct forms of this deficiency have been proposed, namely infantile, juvenile, and adult. National Institutes of Health and ...

). These patients will have all the common features of each individual disease, resulting in a very complex phenotype. Deletions near the distal tip of the

p arm In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total ...

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 Langer–Giedion syndrome (LGS) is a very uncommon autosomal dominant genetic disorder caused by a deletion of a small section of material on chromosome 8. It is named after the two doctors who undertook the main research into the condition in th ...

(caused by deletions of ''

TRPS1 Zinc finger transcription factor Trps1 is a protein that in humans is encoded by the ''TRPS1'' gene. This gene encodes a GATA-like transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the ...

'' and ''

EXT1 Exostosin-1 is a protein that in humans is encoded by the ''EXT1'' gene. This gene encodes one of the two endoplasmic reticulum-resident type II transmembrane glycosyltransferase – the other being EXT2 – which are involved in the chain elong ...

'' on 8q24 and

WAGR syndrome WAGR syndrome (also known as WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome) is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour (a tumour of the kidneys), Aniridia (absence ...

(caused by deletions on

11q13 11Q13, also 11QMelch or the Melchizedek document, is a fragmentary manuscript among the Dead Sea Scrolls ( from Cave 11) which mentions Melchizedek as leader of God's angels in a war in Heaven against the angels of darkness instead of the more fam ...

encompassing ''

PAX6 Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the ''PAX6'' gene. Function PAX6 is a member of the Pax gene family which is responsible for carrying the geneti ...

'' and ''

WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...

''.)

References

{{reflist Genetic syndromes Chromosomal abnormalities