1q21.1 deletion syndrome
1q21.1 deletion syndrome | |
---|---|
Other names | Chromosome 1q21.1 microdeletion syndrome, 1q21.1 microdeletion, Monosomy 1q21.1, Del(1)(q21), 1q21.1 contiguous gene deletion, 1q21.1 deletion, Chromosome 1q21.1 deletion syndrome, Chromosome 1q21.1 deletion syndrome, 1.35-Mb. |
Specialty | Genetics. |
Symptoms | Delayed development, intellectual disability, physical abnormalities, neurological abnormalities and psychiatric problems.[1] |
Usual onset | Infancy.[2] |
Causes | Deletion of genetic material on the long arm (or q arm) of chromosome 1 at position 21.1.[3] |
Diagnostic method | Chromosomal microarray analysis.[4] |
Differential diagnosis | 22q11.2 microdeletion syndrome.[4] |
Frequency | 0.015% of the population.[5] |
1q21.1 deletion syndrome is a rare aberration of chromosome 1. 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. One chromosome has the normal length and the other is too short.
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.
The syndrome is a form of the 1q21.1 copy number variations, and it is a deletion in the distal area of the 1q21.1 part. 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 intellectual impairment and various physical anomalies.[1]
1q21.1 microdeletion is a very rare chromosomal condition. Only 46 individuals with this deletion have been reported in medical literature as of August 2011.[3]
Signs and symptoms
Approximately 75% of all children with a 1q21.1 microdeletion exhibit delayed development, notably in motor skills such as sitting, standing, and walking.[1] Individuals may have generalized mild learning difficulties; about 30% of those diagnosed with 1q21.1 deletion syndrome are affected.[4]
Dysmorphic craniofacial traits are common, however, they are highly varied and thus difficult to identify. Microcephaly has been reported in 39% of those with the 1q21.1 deletion.[4][2]
It is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have completely different effects on members of the same family.[1][4]
The majority of affected people have normal neurologic physical examinations, however hypotonia and tremors are quite common. Seizures affect roughly 16% of children and typically begin during infancy.[1][4]
Possible psychiatric and behavioral abnormalities include
A common deletion is between 1.0-1.9Mb. Mefford states that the standard for a deletion is 1.35Mb.[8]
Causes
1q21.1 deletion is autosomal dominant, with 18%-50% of deletions developing de novo and 50%-82% inherited from a parent.[4][1]
The majority of affected individuals are missing a 1.35 million
The symptoms caused by a 1q21.1 microdeletion are most likely due to the loss of many genes in this region. Researchers are attempting to determine which missing genes may contribute to 1q21.1 deletions' specific characteristics. Because some people with a 1q21.1 microdeletion have no clear associated traits, it is hypothesized that additional genetic and environmental factors influence the development of symptoms.[1]
Due to this genetic misprint, the embryo may experience problems in the development during the first months of pregnancy. Approximately 20 to 40 days after fertilization, something goes wrong in the construction of the body parts and brain, which leads to a chain reaction.[9]
Diagnosis
The recurring distal 1.35-Mb
Differential diagnosis
22q11.2 microdeletion shares several characteristics with 1q21.1 microdeletion including developmental delays, learning disabilities, intellectual disability, and behavioral deviations. Those with recurrent 1q21.1 microdeletion, on the other hand, do not have the distinctive facial traits seen in the 22q11.2 microdeletion syndrome.[4][5]
Management
Several examinations should be performed to determine the level of
Because of the variability in 1q21.1 deletion, management is dependent on specific symptoms. Occupational and physical therapy, as well as special learning programs, may be used to manage symptoms.[4]
Epidemiology
Nonallelic homologous recombination (NAHR), mediated by low copy repeats (LCRs), is a well-known mechanism of copy number alterations in an array of genomic diseases. Individually, these conditions are uncommon, yet collectively, they impact a significant portion of the population. 1q21.1 deletions are estimated to occur in about 0.015% of the population. However, these CNVs are incompletely penetrant, therefore it is likely that the actual prevalence in the general population is greater than the current predictions.[5]
Research
Statistical research showed that schizophrenia is more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome. 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.[10][11]
![](http://upload.wikimedia.org/wikipedia/commons/1/11/Relation_1q21_1.jpg)
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.[12]
Research is done on 10–12 genes on 1q21.1 that produce
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. HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2.[14] Research on the genes CHD1L and PRKAB2 within lymphoblast cells[15] lead to the conclusion that anomalies appear with the 1q21.1-deletion syndrome:
- CHD1L is an enzyme which is involved in untangling the chromatides 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 helicase with the Werner syndrome
- PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.
GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5 tetralogy of Fallot is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common.[16]
References
- ^ a b c d e f g h i "1q21.1 microdeletion: MedlinePlus Genetics". medlineplus.gov. Retrieved 2023-07-25.
- ^ a b "1q21.1 microdeletion syndrome — About the Disease — Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2023-07-25.
- ^ a b "Overview: 1q21.1 microdeletion syndrome". Genetic and Rare Diseases Information Center (GARD). Office of Rare Diseases Research • U.S. National Institutes of Health. 8 August 2011. Archived from the original on 2 June 2013. Retrieved 9 September 2013.
- ^ PMID 21348049– via PubMed.
- ^ PMID 29691480.
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- PMID 18668039.
- PMID 18784092.
- ^ A. Ploeger; 'Towards an integration of evolutionary psychology and developmental science: New insights from evolutionary developmental biology'
- PMID 21285140.
- S2CID 26047827.
- PMID 21383261.
- PMID 19850849.
- PMID 16938426.
- PMID 21824431.
- PMID 22199024.
Further reading
- Genetics of Mental Retardation, Karger. Knight S. (ed) Chapter One: 'A Parent's' Perspective' contains description and photos of female with 1q21.1 microdeletion
- Brunet A, Armengol L, Heine D, et al. (2009). "BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1". BMC Med. Genet. 10: 144. PMID 20030804.
- Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, Sahoo T, et al. (2008). "Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities". Nat Genet. 40 (12): 1466–71. PMID 19029900.
- Crespi B, Stead P, Elliot M (2010). "Evolution in health and medicine Sackler colloquium: Comparative genomics of autism and schizophrenia". Proc Natl Acad Sci U S A. 107 (Suppl 1): 1736–41. PMID 19955444.