Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies. The following chromosome instability syndromes are known: * Ataxia telangiectasia *

Ataxia telangiectasia-like disorder Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

* Bloom syndrome * Fanconi anaemia * Nijmegen breakage syndrome

Neurodegenerative diseases

Chromosome instability syndromes include several inherited neurodegenerative diseases that are due to

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s in genes that encode enzymes necessary for

DNA repair DNA repair is 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 radiation can cause DNA da ...

. Epigenetic alterations often occur in association with the DNA repair defect, and such alterations likely have a role in the

etiology Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...

of the disease. Chromosome instability syndromes due to impaired DNA repair and with features of neurodegeneration and epigenetic alteration were summarized by Bernstein and Bernstein. These syndromes include Aicardi-Goutieres syndrome,

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

, ataxia-telangiectasia,

Cockayne syndrome Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (phot ...

fragile X syndrome Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may ...

, Friedrich's ataxia,

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

, spinocerebellar ataxia type 1, trichothiodystrophy and

xeroderma pigmentosum Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in s ...

Hypogonadism

Genes '' MCM8'' and ''MCM9'' encode proteins that form a complex. This complex functions in

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be ...

and repair of DNA double-strand breaks. Inherited mutations in ''MCM8'' and ''MCM9'' can cause a chromosomal instability syndrome characterized by ovarian failure. The germline MCM8-MCM9 protein complex is most likely required for the resolution of double-strand breaks that occur during

in the pachytene stage of

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately ...

References

{{DNA replication and repair-deficiency disorder