17q21.3 recurrent microdeletion syndrome
Encyclopedia
17q21.31 microdeletion syndrome is a rare genetic disorder
caused by a deletion of a segment of chromosome 17 which contains six genes. This deletion syndrome was discovered independently in 2006 by three different research groups.
at birth, poor feeding in infancy (often requiring feeding by tube for a period) and oromotor dyspraxia together with moderate developmental delays and learning disabilities but amiable behaviour. Other clinically important features include epilepsy
, heart defects (atrial septal defect
, ventricular septal defect
) and kidney/urological anomalies. Silvery depigmentation
of strands of hair have been noted in several patients. With age there is an apparent coarsening of facial features. 17q21.3 was reported simultaneously in 2006 by three independent groups, with each group reporting several patients, , and is now recognised to be one of the more common recurrent microdeletion syndromes. Recently a patient with a small duplication
in same segment of DNA has been described. An overview of the clinical features of the syndrome, by reviewing 22 individuals with a 17q21.31 microdeletion, estimated the disorder is present in one in every 16,000 people.
(Kb) in size encompassing at least six genes, among them the microtubule-associated protein tau (MAPT). A review of five patients found the parental chromosome from which the deletion originated carried a common 900kb inversion polymorphism
. The orientation of low copy repeats flanking the deleted segment, suggests the inversion in the parental chromosome influences the deletion in the child's chromosome via a non-allelic homologous recombination (NAHR) mechanism.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
caused by a deletion of a segment of chromosome 17 which contains six genes. This deletion syndrome was discovered independently in 2006 by three different research groups.
Clinical description
The symptoms associated with this syndrome are variable, but common features include: low birthweight, low muscle toneHypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
at birth, poor feeding in infancy (often requiring feeding by tube for a period) and oromotor dyspraxia together with moderate developmental delays and learning disabilities but amiable behaviour. Other clinically important features include epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, heart defects (atrial septal defect
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
, ventricular septal defect
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
) and kidney/urological anomalies. Silvery depigmentation
Depigmentation
Depigmentation is the lightening of the skin, or loss of pigment. Depigmentation of the skin can be caused by a number of local and systemic conditions. The pigment loss can be partial or complete...
of strands of hair have been noted in several patients. With age there is an apparent coarsening of facial features. 17q21.3 was reported simultaneously in 2006 by three independent groups, with each group reporting several patients, , and is now recognised to be one of the more common recurrent microdeletion syndromes. Recently a patient with a small duplication
Gene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
in same segment of DNA has been described. An overview of the clinical features of the syndrome, by reviewing 22 individuals with a 17q21.31 microdeletion, estimated the disorder is present in one in every 16,000 people.
Origin and Size of Deletion
The recurrent deletion is between 500-650 kilobasesBase pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
(Kb) in size encompassing at least six genes, among them the microtubule-associated protein tau (MAPT). A review of five patients found the parental chromosome from which the deletion originated carried a common 900kb inversion polymorphism
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
. The orientation of low copy repeats flanking the deleted segment, suggests the inversion in the parental chromosome influences the deletion in the child's chromosome via a non-allelic homologous recombination (NAHR) mechanism.
Affected genes
The deletion that causes this disease can remove up to six different genes. These include:- The uncharacterised protein C17orf69 (also known as FLJ25168).
- Corticotropin releasing hormone receptor 1Corticotropin releasing hormone receptor 1Corticotropin releasing hormone receptor 1 is a protein, also known as CRF1, with the latter now being the IUPHAR-recommended name...
(CRHR1, also known as CRF-R, CRF1) - Microtubule-associated protein tau (MAPT)
- The uncharacterised protein KIAA1267KIAA1267Uncharacterized protein KIAA1267 is a protein that in humans is encoded by the KIAA1267 gene.-Interactions:KIAA1267 has been shown to interact with CCDC85B.-Further reading:...
(also known as DKFZP727C091)
External links
- OrphanetOrphanetOrphanet is a European website providing information about orphan drugs and rare diseases. It contains content both for physicians and for patients. Its administrative office is in Paris. The organisation also publishes the open-access online journal Orphanet Journal of Rare Diseases.-External...
entry for 17q21.31 microdeletion syndrome - 17q21.31 microdeletion information leaflet for families from Unique — the rare chromosome disorder support group.