1q21.1 deletion syndrome
Encyclopedia
1q21.1 deletion syndrome or 1q21.1 (recurrent) microdeletion is a rare aberration of chromosome 1. Unique, the international rare chromosome disorder group, has 48 genetically confirmed registered cases of this deletion worldwide (november 2011).
In a common situation a human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the deletion is situated.
Next to the deletion syndrome, there is also a 1q21.1 duplication syndrome
. While there is a part of the DNA missing with the deletion syndrome on a particular spot, there are two or three copies of a similar part of the DNA on the same spot with the duplication syndrome. Literature refers to both the deletion and the duplication as the 1q21.1 copy-number variations (CNV).
The CNV leads to a very variable phenotype
and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of mental retardation and various physical anomalies.
(Mb) (from 141.5 Mb to 147.9 Mb). There are two areas where the deletion can be: the TAR-area for the TAR syndrome
and the distal area for other anomalies. The area has multiple repetitions of the same structure (areas with the same color in the picture have equal structures) Only 25% of the structure is unique. There are several gaps in the sequence. There is no further information available about the DNA-sequence in those areas up till now. The gaps represent approximately 700 Kilobase. New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end markers of a deletion. The area of 1q21.1 is one of the most difficult parts of the human genome to map.
In some cases the deletion is so large that both areas are involved, the so called Class II-deletion. There are some complex cases in which both the TAR area and the distal area are affected, while the area in between is normal. There are also some a-typical variants.
Symptoms that are not confirmed:
It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have complete different effects on members of the same family.
A common deletion is between 1.0–1.9Mb. Mefford states the standard for a deletion is 1.35 Mb. The largest deletion seen on a living human is over 5 Mb.
, TXNIP
, POLR3GL
, LIX1L
, RBM8A
, PEX11B
, ITGA10
, ANKRD35
, PIAS3
, NUDT17, POLR3C
, RNF115, CD160
, PDZK1
, and GPR89A
Genes related to 1q21.1 deletion in the distal area are PDE4DIP
, HYDIN2, PRKAB2
, PDIA3P, FMO5
, CHD1L
, BCL9
, ACP6
, GJA5
, GJA8
, NBPF10
, GPR89B
, GPR89C, PDZK1P1 and NBPF11.
. In this situation, parts of the chromosome may get lost. Accidental changes appear in the chromosome. In the situation of an unequal crossing-over, copy-number variation (CNVs) will appear. These CNVs will lead to deletions or duplications. About 0.4% of the human genome has CNVs, and it is a common process. Such an accidental mutation is called a 'de novo'-situation, and it appears 75% of the cases.
In 25% of the cases, one of the parents is carrier of the syndrome, without any effect on the parent. Sometimes adults have mild problems with the syndrome. To find out whether either of the parents carries the syndrome, both parents have to be tested. In several cases, the syndrome was identified with the child, because of an autism disorder or another problem, and later it appeared that the parent was affected as well. The parent never knew about it up till the moment that the DNA-test proved the parent to be a carrier.
In families where both parents have been tested negative on the syndrome, chances on a second child with the syndrome are extremely low. If the syndrome was found in the family, chances on a second child with the syndrome are 50%, because the syndrome is autosomal dominant. The effect of the syndrome on the child cannot be predicted.
The Syndrome can be detected with fluorescence in situ hybridization and Affymetrix GeneChip Operating Software
.
For parents with a child with the syndrome, it is advisable to consult a physician before a next pregnancy and to do prenatal screening.
Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.
Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.
It appears that there is a relation between autism
and schizophrenia
. Both autism and schizophrenia are caused by problems of the development of the embryo during the first month of pregnancy. Within 20 to 40 days after the conception, something goes wrong in the development of the embryo in the construction of both the body and the brain, which starts a chain reaction. Both diseases have the same cause.
In the genetic area, relations have been found between both autism and schizophrenia based on duplications and deletions of chromosomes. Statistical research showed that schizophrenia is significantly more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome
. Similar observations were done for chromosome 16 on 16p11.2 (deletion: autism/duplication: schizophrenia), chromosome 22 on 22q11.21 (deletion (Velo-cardio-facial syndrome): schizophrenia/duplication: autism) and 22q13.3 (deletion (Phelan-McDermid syndrome): schizophrenia/duplication: autism). Further research confirmed that the odds on a relation between schizophrenia and deletions at 1q21.1, 3q29, 15q13.3, 22q11.21 en Neurexin 1 (NRXN1) and duplications at 16p11.2 are at 7.5% or higher.
Research on autism/schizophrenia relations for chromosome 15 (15q13.3), chromosome 16 (16p13.1), and chromosome 17 (17p12) on the subject of deletions/duplications are still inconclusive.
Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder.
Research is done on 10–12 genes on 1q21.1 that produce DUF1220
-locations. DUF1220 is an unknown protein
, which is active in the neuron
s of the brain
near the neocortex
. Based on research on apes and other mammals, it is assumed that DUF1220 is related to cognitive development (man: 212 locations; chimpanzee: 37 locations; monkey: 30 locations; mouse: 1 location). It appears that the DUF1220-locations on 1q21.1 are in areas that are related to the size and the development of the brain. The aspect of the size and development of the brain is related to autism (macrocephaly
) and schizophrenia (microcephaly
). It is assumed that a deletion or a duplication of a gene that produces DUF1220-areas, might cause growth and development disorders in the brain
Another relation between macrocephaly
with duplications and microcephaly
with deletions has been seen in research on the HYDIN Paralog or HYDIN2. This part of 1q21.1 is involved in the development of the brain. It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. The HYDIN2 is a copy of the HYDIN found on 16q22.2.
Research on the genes CHD1L and PRKAB2 within lymphoblast
cells lead to the conclusion that anomalies appear with the 1q21.1-deletionsyndrome:
In a common situation a human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. In 1q21.1, the '1' stands for chromosome 1, the 'q' stands for the long arm of the chromosome and '21.1' stands for the part of the long arm in which the deletion is situated.
Next to the deletion syndrome, there is also a 1q21.1 duplication syndrome
1q21.1 duplication syndrome
1q21.1 duplication syndrome or 1q21.1 microduplication is a rare aberration of chromosome 1. , the international rare chromosome disorder group, has 38 genetically confirmed registered cases of this duplication worldwide ....
. While there is a part of the DNA missing with the deletion syndrome on a particular spot, there are two or three copies of a similar part of the DNA on the same spot with the duplication syndrome. Literature refers to both the deletion and the duplication as the 1q21.1 copy-number variations (CNV).
The CNV leads to a very variable phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of mental retardation and various physical anomalies.
The structure of 1q21.1
The structure of 1q21.1 is complex. The area has a size of approximately 6 MegabaseBase 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...
(Mb) (from 141.5 Mb to 147.9 Mb). There are two areas where the deletion can be: the TAR-area for the TAR syndrome
TAR syndrome
TAR Syndrome is a rare genetic disorder that is characterized by the absence of the radius bone in the forearm, and a dramatically reduced platelet count...
and the distal area for other anomalies. The area has multiple repetitions of the same structure (areas with the same color in the picture have equal structures) Only 25% of the structure is unique. There are several gaps in the sequence. There is no further information available about the DNA-sequence in those areas up till now. The gaps represent approximately 700 Kilobase. New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end markers of a deletion. The area of 1q21.1 is one of the most difficult parts of the human genome to map.
Typing
A common deletion is restricted to the TAR area or the distal area. This is a Class I-deletion.In some cases the deletion is so large that both areas are involved, the so called Class II-deletion. There are some complex cases in which both the TAR area and the distal area are affected, while the area in between is normal. There are also some a-typical variants.
Symptoms
Recognised symptoms up till now are:- only one set of genes on the two chromosomes function (HaploinsufficiencyHaploinsufficiencyHaploinsufficiency occurs when a diploid organism only has a single functional copy of a gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state...
) - TAR syndromeTAR syndromeTAR Syndrome is a rare genetic disorder that is characterized by the absence of the radius bone in the forearm, and a dramatically reduced platelet count...
- Neurological-psychiatric problems: AutismAutismAutism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
; SchizophreniaSchizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
; epilepsyEpilepsyEpilepsy 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...
; learning problems; Mental retardation — mild to moderate; Developmental delay — mild to moderate (milestones like sitting, standing and walking come at a later period in childhood); Children show an ataxic gait and fall down a lot - Dysmorphism: Slightly unusual facial appearance; disturbed growth; skeletal malformations; Small head (microcephalyMicrocephalyMicrocephaly 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...
); Prominent forehead; Bulbous nose; Deep-set eyes; Broad thumbs; Broad toes; Squint; Very flexible joints; Clavicular pseudoarthrosis (the collarbone doesn't develop normally) (Class II-deletion); An extra transverse crease of the fifth finger (Class II-deletion)); Problems with the development of the vagina (Müllerian aplasiaAplasiaAplasia is defined in general as "defective development or congenital absence of an organ or tissue." In the field of hematology, the term refers to "incomplete, retarded, or defective development, or cessation of the usual regenerative process."-Examples:*Acquired pure red cell aplasia*Aplasia...
) - Eyes: Cataracts
- Heart abnormalities and cardiovascular anomalies (30% of the cases): Anomalous origin of the coronary artery (Class II-deletion)
- Kidneys: kidney missing or floating kidneys
- Cancer: NeuroblastomaNeuroblastomaNeuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
- Sleep disturbances
Symptoms that are not confirmed:
- Families with children who have 1q21.1 deletion syndrome report reflux (GERDGastroesophageal reflux diseaseGastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...
) - There is recent information in which Noncompaction cardiomyopathyNoncompaction cardiomyopathyNon-compaction cardiomyopathy , also called spongiform cardiomyopathy, is a rare congenital cardiomyopathy that affects both children and adults. It results from the failure of myocardial development during embryogenesis....
has been seen in combination with a ClassII-deletion. - During a pregnancy increased nunchal translucency and oligohydramnion were detected.
It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have complete different effects on members of the same family.
A common deletion is between 1.0–1.9Mb. Mefford states the standard for a deletion is 1.35 Mb. The largest deletion seen on a living human is over 5 Mb.
Related genes
Genes related to 1q21.1 deletion in the TAR area are HFE2Hemojuvelin
Hemojuvelin is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis in humans, a severe form of hemochromatosis. In humans, the hemojuvelin protein is encoded by the HFE2 gene...
, TXNIP
TXNIP
Thioredoxin-interacting protein is a protein that in humans is encoded by the TXNIP gene.-Interactions:TXNIP has been shown to interact with Thioredoxin and ZBTB32.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome...
, POLR3GL
POLR3GL
Polymerase III polypeptide G -like also known as POLR3GL is a protein which in humans is encoded by the POLR3GL gene.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome...
, LIX1L
LIX1L
Lix1 homolog -like also known as LIX1L is a protein which in humans is encoded by the LIX1L gene.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome...
, RBM8A
RBM8A
RNA-binding protein 8A is a protein that in humans is encoded by the RBM8A gene.-Interactions:RBM8A has been shown to interact with IPO13, MAGOH and UPF3A.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome...
, PEX11B
PEX11B
Peroxisomal membrane protein 11B is a protein that in humans is encoded by the PEX11B gene. It is involved in the regulation of peroxisome abundance.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome...
, ITGA10
ITGA10
Integrin alpha-10 also known as ITGA10 is a protein that in humans is encoded by the ITGA10 gene.-Function:Integrins are integral membrane proteins composed of an alpha chain and a beta chain, and are known to participate in cell adhesion as well as cell-surface mediated signalling...
, ANKRD35
ANKRD35
Ankyrin repeat domain 35 also known as ANKRD35 is a protein which in humans is encoded by the ANKRD35 gene.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome...
, PIAS3
PIAS3
E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene.-Interactions:PIAS3 has been shown to interact with GFI1, RELA, Mothers against decapentaplegic homolog 3, Microphthalmia-associated transcription factor, HMGA2 and Mothers against decapentaplegic homolog...
, NUDT17, POLR3C
POLR3C
DNA-directed RNA polymerase III subunit RPC3 is an enzyme that in humans is encoded by the POLR3C gene.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome-Further reading:...
, RNF115, CD160
CD160
CD160 antigen is a protein that in humans is encoded by the CD160 gene.-Related gene problems:*TAR syndrome*1q21.1 deletion syndrome*1q21.1 duplication syndrome...
, PDZK1
PDZK1
Na/H exchange regulatory cofactor NHE-RF3 is a protein that in humans is encoded by the PDZK1 gene.-Interactions:PDZK1 has been shown to interact with AKAP10, FARP2, Sodium-hydrogen antiporter 3 regulator 1, SLC22A12, SLK, SLC22A4, CLCN3, PDZK1IP1, Cystic fibrosis transmembrane conductance...
, and GPR89A
Genes related to 1q21.1 deletion in the distal area are PDE4DIP
PDE4DIP
Myomegalin also known as phosphodiesterase 4D-interacting protein or cardiomyopathy-associated protein 2 is a protein that in humans is encoded by the PDE4DIP gene.-Further reading:...
, HYDIN2, PRKAB2
PRKAB2
5'-AMP-activated protein kinase subunit beta-2 is an enzyme that in humans is encoded by the PRKAB2 gene.-Interactions:PRKAB2 has been shown to interact with PRKAG2 and PRKAG1.-Further reading:...
, PDIA3P, FMO5
FMO5
Dimethylaniline monooxygenase [N-oxide-forming] 5 is an enzyme that in humans is encoded by the FMO5 gene.-Further reading:...
, CHD1L
CHD1L
Chromodomain-helicase-DNA-binding protein 1-like is an enzyme that in humans is encoded by the CHD1L gene. It has been implicated in chromatin remodeling and DNA relaxation process required for DNA replication, repair and transcription....
, BCL9
BCL9
B-cell CLL/lymphoma 9 protein is a protein that in humans is encoded by the BCL9 gene.Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder. -Further reading:...
, ACP6
ACP6
Lysophosphatidic acid phosphatase type 6 is an enzyme that in humans is encoded by the ACP6 gene.-Interactions:ACP6 has been shown to interact with Integrin-linked kinase.-Further reading:...
, GJA5
GJA5
Gap junction alpha-5 protein is a protein that in humans is encoded by the GJA5 gene.- Function :This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of...
, GJA8
GJA8
Gap junction alpha-8 protein is a protein that in humans is encoded by the GJA8 gene. It is also known as connexin 50.-Interactions:GJA8 has been shown to interact with Tight junction protein 1....
, NBPF10
NBPF10
Neuroblastoma breakpoint family member 10 is a protein that in Homo sapiens is encoded by the NBPF10 gene.The full gene is 75,313 bp, with the major isoform of mRNA being 10,697 bp long. The gene is located at 1q21.1. NBPF contains what is known as the DUF1220 repeats. The highly conserved,...
, GPR89B
GPR89B
Protein GPR89 is a protein that in humans is encoded by the GPR89B gene.-Further reading:...
, GPR89C, PDZK1P1 and NBPF11.
Diagnostics
The syndrome may appear in cases where neither of the parents carries the genes. Because of the repetitions in 1q21.1, there is a larger chance on an unequal crossing-over during meiosisMeiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
. In this situation, parts of the chromosome may get lost. Accidental changes appear in the chromosome. In the situation of an unequal crossing-over, copy-number variation (CNVs) will appear. These CNVs will lead to deletions or duplications. About 0.4% of the human genome has CNVs, and it is a common process. Such an accidental mutation is called a 'de novo'-situation, and it appears 75% of the cases.
In 25% of the cases, one of the parents is carrier of the syndrome, without any effect on the parent. Sometimes adults have mild problems with the syndrome. To find out whether either of the parents carries the syndrome, both parents have to be tested. In several cases, the syndrome was identified with the child, because of an autism disorder or another problem, and later it appeared that the parent was affected as well. The parent never knew about it up till the moment that the DNA-test proved the parent to be a carrier.
In families where both parents have been tested negative on the syndrome, chances on a second child with the syndrome are extremely low. If the syndrome was found in the family, chances on a second child with the syndrome are 50%, because the syndrome is autosomal dominant. The effect of the syndrome on the child cannot be predicted.
The Syndrome can be detected with fluorescence in situ hybridization and Affymetrix GeneChip Operating Software
Affymetrix GeneChip Operating Software
Affymetrix GeneChip Operating Software is a software system for managing Affymetrix microarray data. It captures and analyzes the array images, provides workflow tracking of data, manages experiment data, and carries out basic expression analysis....
.
For parents with a child with the syndrome, it is advisable to consult a physician before a next pregnancy and to do prenatal screening.
Management
Treatment of cause: Due to the genetic cause, no treatment of the cause is possible.Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.
Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.
Research
On several locations in the world people are studying on the subject of 1q21.1 deletion syndrome. The syndrome was identified for the first time with people with heart abnormalities. The syndrome has later been found with patients with autism and schizophrenia. Research is done on patients with a symptom of the syndrome, to find more patients with the syndrome.It appears that there is a relation between autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. Both autism and schizophrenia are caused by problems of the development of the embryo during the first month of pregnancy. Within 20 to 40 days after the conception, something goes wrong in the development of the embryo in the construction of both the body and the brain, which starts a chain reaction. Both diseases have the same cause.
In the genetic area, relations have been found between both autism and schizophrenia based on duplications and deletions of chromosomes. Statistical research showed that schizophrenia is significantly more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome
1q21.1 duplication syndrome
1q21.1 duplication syndrome or 1q21.1 microduplication is a rare aberration of chromosome 1. , the international rare chromosome disorder group, has 38 genetically confirmed registered cases of this duplication worldwide ....
. Similar observations were done for chromosome 16 on 16p11.2 (deletion: autism/duplication: schizophrenia), chromosome 22 on 22q11.21 (deletion (Velo-cardio-facial syndrome): schizophrenia/duplication: autism) and 22q13.3 (deletion (Phelan-McDermid syndrome): schizophrenia/duplication: autism). Further research confirmed that the odds on a relation between schizophrenia and deletions at 1q21.1, 3q29, 15q13.3, 22q11.21 en Neurexin 1 (NRXN1) and duplications at 16p11.2 are at 7.5% or higher.
Research on autism/schizophrenia relations for chromosome 15 (15q13.3), chromosome 16 (16p13.1), and chromosome 17 (17p12) on the subject of deletions/duplications are still inconclusive.
Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder.
Research is done on 10–12 genes on 1q21.1 that produce DUF1220
DUF1220
DUF1220 is a protein domain of unknown function that shows a striking human-specific increase in copy number and may be important to human brain evolution. The copy number of DUF1220 domains increases generally as a function of a species evolutionary proximity to humans. DUF1220 copy number is...
-locations. DUF1220 is an unknown protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, which is active in the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
near the neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
. Based on research on apes and other mammals, it is assumed that DUF1220 is related to cognitive development (man: 212 locations; chimpanzee: 37 locations; monkey: 30 locations; mouse: 1 location). It appears that the DUF1220-locations on 1q21.1 are in areas that are related to the size and the development of the brain. The aspect of the size and development of the brain is related to autism (macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
) and schizophrenia (microcephaly
Microcephaly
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...
). It is assumed that a deletion or a duplication of a gene that produces DUF1220-areas, might cause growth and development disorders in the brain
Another relation between macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
with duplications and microcephaly
Microcephaly
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...
with deletions has been seen in research on the HYDIN Paralog or HYDIN2. This part of 1q21.1 is involved in the development of the brain. It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. The HYDIN2 is a copy of the HYDIN found on 16q22.2.
Research on the genes CHD1L and PRKAB2 within lymphoblast
Lymphoblast
Lymphoblasts are immature cells which typically differentiate to form mature lymphocytes. Normally lymphoblasts are found in the bone marrow, but in acute lymphoblastic leukemia , lymphoblasts proliferate uncontrollably and are found in large numbers in the peripheral blood.The size is between 10...
cells lead to the conclusion that anomalies appear with the 1q21.1-deletionsyndrome:
- CHD1L is an enzyme which is involved in untangling the chromatidChromatidA chromatid is one of the two identical copies of DNA making up a duplicated chromosome, which are joined at their centromeres, for the process of cell division . They are called sister chromatids so long as they are joined by the centromeres...
es and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicaseHelicaseHelicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
with the Werner syndromeWerner syndromeWerner syndrome is a very rare, autosomal recessive disorder characterized by the appearance of premature aging.... - PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.
Further reading
- Bringing Up a Challenging Child at Home: When Love is not Enough by Jane Gregory, published by Jessica Kingsley, London. Subject was diagnosed with a 1q21.1 microdeletion after publication
- Genetics of Mental Retardation, Karger. Knight S. (ed) Chapter One: 'A Parent's' Perspective' contains description and photos of female with 1q21.1 microdeletion
External links
- 1q21.1 microdeletions
- GeneReviews NCBI Bookshelf
- Orpha.net
- Blogs on children with 1q21.1 deletion syndrome Chrissy, Laura and Niko