14q21.3 Deletion
What is 14q21.3 Deletion?
A rare disease known as 14q21.3 deletion syndrome is caused by a lack of genetic information at this chromosome location. Genes are the blueprint for everything that the body needs to function, and are found in the cell nucleus as highly compacted chromosomes. Humans have 23 pairs of chromosomes, one inherited from each parent at birth, with the first 22 encoding general bodily information and a 23rd pair known as the sex chromosomes. Geneticists refer to locations within the chromosomes to better find individual genes by their location. The location code used to denote gene location can be broken down as follows:
- An initial number that refers to the chromosome, from 1-22 autosomes and either X or Y for the sex chromosomes.
- A letter that refers to the section or arm of that chromosome, p is short and q is long.
- Another number that matches the band, either light or dark, on a particular pattern of stained bands of the chromosome.
- Decimal points indicate sub-bands within either a light or dark area.
In the case of this syndrome, the affected gene lies on chromosome 14, the long arm (q), the 21st band, and a second sub-band within the 3rd banding pattern.
The deletion of 14q21.3 is a very rare condition that affects so few people that there is not a lot of information on this specific type of deletion. However, more general deletions occurring in the 14th chromosome have been studied due to their association with childhood development of oligodendroglioma. This refers to a rare type of brain tumor that develops from glial cells called oligodendrocytes, often from fatty tissue that is supposed to protect the nerve cells in the brain. The development of oligodendroglioma in children is very rare, and has prompted a genetic investigation to find out common causes of this tumor development. While 14q21.3 deletion may not be the specific cause, it likely contributes to oligodendroglioma or is a portion of the deletion of the 14th chromosome.
A rare disease known as 14q21.3 deletion syndrome is caused by a lack of genetic information at this chromosome location. Genes are the blueprint for everything that the body needs to function, and are found in the cell nucleus as highly compacted chromosomes. Humans have 23 pairs of chromosomes, one inherited from each parent at birth, with the first 22 encoding general bodily information and a 23rd pair known as the sex chromosomes. Geneticists refer to locations within the chromosomes to better find individual genes by their location. The location code used to denote gene location can be broken down as follows:
- An initial number that refers to the chromosome, from 1-22 autosomes and either X or Y for the sex chromosomes.
- A letter that refers to the section or arm of that chromosome, p is short and q is long.
- Another number that matches the band, either light or dark, on a particular pattern of stained bands of the chromosome.
- Decimal points indicate sub-bands within either a light or dark area.
In the case of this syndrome, the affected gene lies on chromosome 14, the long arm (q), the 21st band, and a second sub-band within the 3rd banding pattern.
The deletion of 14q21.3 is a very rare condition that affects so few people that there is not a lot of information on this specific type of deletion. However, more general deletions occurring in the 14th chromosome have been studied due to their association with childhood development of oligodendroglioma. This refers to a rare type of brain tumor that develops from glial cells called oligodendrocytes, often from fatty tissue that is supposed to protect the nerve cells in the brain. The development of oligodendroglioma in children is very rare, and has prompted a genetic investigation to find out common causes of this tumor development. While 14q21.3 deletion may not be the specific cause, it likely contributes to oligodendroglioma or is a portion of the deletion of the 14th chromosome.
This genetic deletion in chromosome 14 is so rare that only a few cases have been reported. In one case study, 12 children were affected by various deletions in their chromosome 14, but only one of them contained the described deletion 14q21.3.
While the exact rare disease symptoms caused by a 14q21.3 deletion is unknown, the cause is this namesake genetic deletion on chromosome 14. This is a random mutation that occurs in offspring spontaneously, and is not inherited genetically from the parents. There are currently so few cases of 14q21.3 deletion that it is difficult to study the effects on the body. However, there are a few gene candidates in this region of the chromosome that if deleted, would have a negative impact on development:
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NRXN3 - This gene helps to improve connections between neurons in the brain, and its deletion reduces the release of neurotransmitters that carry important information in the brain.
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DIO2 - This gene is expressed in glial cells, and it is hypothesized that deletion of this gene leads to dysregulated glial cells that can form oligodendrogliomas.
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TSHR - The thyroid stimulating hormone receptor (TSHR) is responsible for identifying and carrying signals into the thyroid gland to produce the proper hormones for the body. A deletion of this gene could cause a dysfunctional thyroid.
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GTF2A1 - This gene produces transcription factors that are necessary for RNA polymerase to read and translate RNA into proteins.
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STON2 – The stonin 2 gene encodes a protein that interacts with endocytic machinery proteins EPS15 and intersectin-1 to allow for vesicle endocytosis. This means that these genes are responsible for regulating what is able to enter the cell. Lack of regulation may lead to schizophrenia and tumor progression.
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SEL1L – This gene encodes a transmembrane protein found in the endoplasmic reticulum of the cell that is involved in recruiting and translocating substrates of the ER for degradation. This plays an important role in maintaining cell health, and without this gene the cell can undergo transformations that lead to tumor progression.
The symptoms caused by 14q21.3 deletion are not well defined due to a small number of individuals who are affected. However, the appearance of oligodendrogliomas in children is very rare, and many studies have concluded that a deletion somewhere in the 14th chromosome is likely the cause of childhood brain tumor development. One clinical case study connected a 14q21.3 deletion with a glioma tumor present in the frontal lobe of a child’s brain.
While the specific symptoms to this 14q21.3 deletion are not well defined, some symptoms have been identified for more general chromosome 14 deletions. These may include:
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Minor abnormalities of the hands and feet
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Lip and mouth abnormalities such as cleft lip and palate that make eating, nursing, and talking difficult in young children
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Low muscle tone (hypotonia)
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Abnormal appearance or development of the face, head, and genitals
Additionally, there are medical concerns that may be associated with this deletion that should be monitored for treatment:
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Difficulty growing or gaining weight
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Abnormal development of the brain or central nervous system (CNS)
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Thyroid dysfunction
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Seizures - very rarely associated with this disease
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Heart conditions
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Respiratory problems
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Kidney problems
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Hearing and vision impairment
A diagnosis of 14q21.3 deletion depends on a genetic screen to determine if an individual lacks this specific locus in their 14th chromosome. This can be conducted by either karyotyping - the analysis of chromosomes for their length and appearance - or using genomic sequencing - the analysis of specific genes within chromosomes.
The appearance of oligodendrogliomas or other growth abnormalities in young children may indicate the need to seek a medical diagnosis. Before genetic testing, all other potential causes of brain tumors should be explored and ruled out.
Currently, there is no cure or specific treatment for 14q21.3 deletion. Treatment is determined on an individual case basis based on symptoms:
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Thyroid dysfunction – thyroxine replacement
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Cleft lip/palate – minor surgery
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Feeding tubes or laxatives to treat gastrointestinal problems that may arise and to improve weight gain when necessary
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Hypotonia – physiotherapy to increase muscle mass
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Abnormal development of different body parts – can be corrected by surgery if influencing quality of life
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Seizures – anti-epileptic medication
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Heart conditions – surgery
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Respiratory problems – surgery and extra oxygen provided during recovery
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Kidney problems – may require surgery or other forms of treatment in the event of obstruction
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Hearing and eyesight – drainage of the ear canal may improve hearing, and vision impairment can be corrected
Depending on the range and severity of symptoms, most young children with 14q21.3 deletion live healthy lives. If the basis of diagnosis is the identification of an oligodendroglioma in the child’s brain, surgery may be required to enable normal development.
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https://rarediseases.info.nih.gov/diseases/3722/chromosome-14q-deletion
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Dichamp, C., Taillibert, S., Aguirre-Cruz, L. et al. Loss of 14q Chromosome in Oligodendroglial and Astrocytic Tumors. J Neurooncol 67, 281–285 (2004). https://doi.org/10.1023/B:NEON.0000024218.68120.8d
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Nauen D, Haley L, Lin MT, Perry A, Giannini C, Burger PC, Rodriguez FJ. Molecular Analysis of Pediatric Oligodendrogliomas Highlights Genetic Differences with Adult Counterparts and Other Pediatric Gliomas. Brain Pathol. 2016 Mar;26(2):206-14. doi: 10.1111/bpa.12291. Epub 2015 Aug 14. PMID: 26206478; PMCID: PMC4724334.
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Rui Zhang, HanXiao Jiang, YuanJie Liu, GuiQiong He, Structure, function, and pathology of Neurexin-3, Genes & Diseases, 2022, ISSN 2352-3042, https://doi.org/10.1016/j.gendis.2022.04.008
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https://www.sciencedirect.com/topics/medicine-and-dentistry/dio2
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https://jmg.bmj.com/content/39/2/81
Last updated 12 Oct 2017, 09:07 PM
12 Oct 2017, 09:07 PM
Hey Brandon.
My son is 3,8 years old he have a 14q 21.3 deletion. I´m looking every where on the internet to find something more about it...
I would love to hear from you..
18 Apr 2017, 02:08 PM
Our son, who is now 3 1/2 years old has been diagnosed with a deleted chromosome and has also been diagnosed as Autistic. I am not having too much luck finding information on this particular chromosome deletion and am wondering if there are others dealing with this same issue or who may have any knowledge of it.
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My son was born the 8 of jan. 2014
He has an 14q 21.3 deletion. We are hopping to find other people with these deletion in here.
Blessed parent that is looking for answers and connections. Our son has a rare chromsome deletion 14q21.3. Trying to find a common thread and make connections with other parents to possible work...
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Chromosone 14q21.3 deletion
Created by Brandon Dill | Last updated 12 Oct 2017, 09:07 PM
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