Nijmegen breakage syndrome
Encyclopedia
Nijmegen breakage syndrome (NBS), also known as Berlin breakage syndrome and Seemanova syndrome, is a rare autosomal
recessive congenital disorder
causing chromosomal instability, probably as a result of a defect in the Double Holliday junction
DNA repair
mechanism.
NBS1 codes for a protein that has two major functions: (1) to stop the cell cycle in the S phase, when there are errors in the cell DNA (2) to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of Dna repair. This explains clearly that mutations in the NBS1 gene lead to higher levels of cancer (see Fanconi anemia, cockayne syndrome...)
The name derives from the Dutch city Nijmegen where the condition was first described.
Most people with NBS have West Slavic origins
. The largest number of them live in Poland
.
Mrs.Seemanova MD after whom the name of the syndrome was given, currently works at Motol Hospital, Prague, Czech Republic, as a Professor of medical genetics.
, a distinct facial appearance, short stature, immunodeficiency
, radiation sensitivity and a strong predisposition to lymphoid malignancy.
NBS is caused by a mutation
in the NBS1 gene
, located at human chromosome
8q21
. The disease is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome
(chromosome 8 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
causing chromosomal instability, probably as a result of a defect in the Double Holliday junction
Holliday junction
A Holliday junction is a mobile junction between four strands of DNA. The structure is named after Robin Holliday, who proposed it in 1964 to account for a particular type of exchange of genetic information he observed in yeast known as homologous recombination...
DNA repair
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
mechanism.
NBS1 codes for a protein that has two major functions: (1) to stop the cell cycle in the S phase, when there are errors in the cell DNA (2) to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of Dna repair. This explains clearly that mutations in the NBS1 gene lead to higher levels of cancer (see Fanconi anemia, cockayne syndrome...)
The name derives from the Dutch city Nijmegen where the condition was first described.
Most people with NBS have West Slavic origins
West Slavs
The West Slavs are Slavic peoples speaking West Slavic languages. They include Poles , Czechs, Slovaks, Lusatian Sorbs and the historical Polabians. The northern or Lechitic group includes, along with Polish, the extinct Polabian and Pomeranian languages...
. The largest number of them live in Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
.
Mrs.Seemanova MD after whom the name of the syndrome was given, currently works at Motol Hospital, Prague, Czech Republic, as a Professor of medical genetics.
Characteristics
It is characterized by microcephalyMicrocephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
, a distinct facial appearance, short stature, immunodeficiency
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
, radiation sensitivity and a strong predisposition to lymphoid malignancy.
Cause and Genetics
NBS is caused by a mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in the NBS1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, located at human chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
8q21
Chromosome 8 (human)
Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 145 million base pairs and represents between 4.5 and 5.0% of the total DNA in cells....
. The disease is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
(chromosome 8 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
Genetic carrier
A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
External links
- http://www.nijmegenbreakagesyndrome.net/homepage.htm