1q21.1 deletion syndrome

The 1q21.1 - deletion syndrome is a rare disease, which is caused by a deletion in the human chromosome 1 at the location 1q21.1. Consequences of this modification can be mental retardation and various physical anomalies. The penetrance, that is the individual expression of these gene defects is highly variable. Some people with this deletion have no discernible impact.

Unique, an international association of people with rare chromosomal abnormalities knows 64 people registered with this deletion world. (October 2012)

In addition to the 1q21.1 - 1q21.1 deletion there is a duplication, in which the portion in question is present in two or three times.

Structure of the region 1q21.1

The structure of the 1q21.1 is complex. The area has a size of approximately 6 million base pairs ( Mb ) (from 141.5 to 147.9 Mb). There are two areas where the deletion can occur: the TAR region with the sequence of the TAR syndrome and the distal portion of the leads to other abnormalities. The area has a number of repetitions of the same structure ( areas of the same color in the picture have the same structures). Only 25% of the specific structure. To date, there are, however, no complete information on the nucleotide sequence in these regions. The region 1q21.1 is considered one of the most difficult in mapping the human genome. The missing areas are currently at about 700,000 base pairs. Therefore, it is hard to start and end a deletion to determine exactly.


A distinction is made in the 1q21.1 deletion syndrome - two types:

  • The so-called class I deletion is restricted to the TAR region or the distal region.
  • If the deletion so great that both areas are affected, it is called a class II deletion. There are complex cases in which both the tar and the distal portion are affected, while the intermediate area is normal, as well as some atypical variants.

A normal deletion relates to from 1.0 to 1.9 million base pairs ( Mb). After Mefford are 1.35 Mb standard for such deletion. The largest observed on living human deletion is more than 5 Mb


The consequences of microdeletions are phenotypically very variable. While some people have with this syndrome no visible impairments, it comes with other significant limitations. Until now proven symptoms are:

  • Haploinsufficiency
  • TAR syndrome
  • Neurological- psychiatric problems: developmental retardation, mental retardation, autism, schizophrenia, epilepsy, gait with tendency to fall ataxische
  • Dysmorphic features: microcephaly, prominent forehead, bulbous nose, broad thumbs and toes, additional transverse crease of the fifth finger ( class II deletion ), hypermobility of the joints, nonunion of the clavicle ( class II deletion ), vaginal aplasia ( " Mullerian aplasia " )
  • Cardiac abnormalities and cardiovascular anomalies (30 % of cases) as an anomalous origin of the coronary arteries ( class II deletion )
  • Ophthalmological problems: cataracts, deep-set eyes, strabismus
  • Kidney disease: lack of kidney, floating kidney, neuroblastoma

The following symptoms could previously not be safely assigned to the 1q21.1 deletion syndrome -:

  • Reflux of stomach acid into the esophagus
  • Non- compaction cardiomyopathy associated with a class II 1q21.1 deletion syndrome.
  • Increased nuchal translucency and oligohydramnios during pregnancy.

Since little information about the syndrome are present, the completeness of the above list of symptoms is uncertain.

Affected genes

The affected genes in the 1q21.1 deletion syndrome - TAR range are: HFE2 ( Hämojuvelin ), TXNIP, POLR3GL, LIX1L, RBM8A, PEX11B, ITGA10, ANKRD35, PIAS3, NUDT17, POLR3C, RNF115, CD160, PDZK1 and GPR89A.

The affected genes in the distal region are PDE4DIP, HYDIN2, PRKAB2, PDIA3P, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, NBPF10, GPR89B, GPR89C, PDZK1P1 and NBPF11.


The syndrome can also in families where neither of the parents carries the genes occur. Due to the repetition in 1q21.1, there is a higher probability for an unequal crossing-over during meiosis. In this case, parts of the chromosome may be lost and there is copy number variations ( copy number variation - CNV) in the form of deletions or duplications. Thus, a random mutation is called a " de novo " situation and occurs in 75 % of cases.

In 25% of cases is one of the parents is carrier of the syndrome, without it affecting the person or with only mild symptoms. In several cases, the syndrome was first diagnosed in children due to autism or other problem and only later turned out that one of the parents was affected.

In families where both parents tested negative for the syndrome, the risk that a second child comes with the syndrome to the world, is extremely low. If the syndrome has been found in the family, there is a risk of disease by 50% because an autosomal dominant inheritance is present. However, the impact of 1q21.1 microdeletion on - the child can not be predicted. Parents whose child is ill with syndrome should therefore be human genetic advice and examined before a further pregnancy.

A determination of chromosome alteration is by fluorescence in situ hybridization (FISH ) is possible. In pregnancy, a determination is also possible in the context of prenatal diagnosis.


Due to the genetic cause a causative treatment is not possible. However, is indicated is a symptomatic therapy, in particular the correction of deformities occurring and the treatment of comorbidities.


The syndrome was first diagnosed in people with heart abnormalities, but later also found in patients suffering from autism and schizophrenia. Because scientific studies showed that 20 of 1000 patients with autism have a 1q21.1 microdeletion -.

The 1q21.1 deletion syndrome, is currently being investigated at several locations worldwide. There are evidence of an association between autism and schizophrenia, which could have duplications and deletions of chromosomes originated in embryogenesis. Statistical studies have shown that schizophrenia is significantly more common in a 1q21.1 microdeletion -. In contrast, autism is significantly higher with 1q21.1 - Mikroduplizierung. Similar observations were made with regard to chromosome 16 at 16p11.2 ( deletion: Autism / duplication: schizophrenia ) and on chromosome 22 ( 22q11.21 deletion ( Velo- Cardio - Facial Syndrome ): Schizophrenia / duplication: autism) and 22q13.3 ( deletion ( Phelan - McDermid syndrome): Autism: schizophrenia / duplication ) made ​​. Further studies confirm a minimum 7.5 % chance of a link between schizophrenia and deletions on 1q21.1, 3q29, 15q13.3, 22q11.21 s neurexin 1 ( NRXN1 ) and duplication on 16p11.2.

Studies on the relationships between autism, schizophrenia and micro changes on chromosome 15 ( 15q13.3 ) and on chromosome 16 ( 16p13.1 ) and chromosome 17 ( 17p12 ) are not yet conclusive (as of 2011 ).

Variations in the BCL9 gene, which is located in the distal region, increase the risk of schizophrenia and may lead to bipolar disorder, and depression.

The research currently focuses on ten to twelve genes on 1q21.1, which are responsible for the production of DUF1220. DUF1220 is a protein domain of unknown function which is active in the area of the neocortex in the neurons of the brain. Based on studies in monkeys and other mammals, it is assumed that the number of DUF1220 gene loci with cognitive development is related ( human: 212; Chimpanzee: 37; monkeys: 30; mouse: 1). It seems that the DUF1220 - places are located on 1q21.1 in places that are associated with the size and development of the brain, which in turn with autism ( macrocephaly ) and schizophrenia ( microcephaly ) is connected. It is assumed that a deletion or duplication of a gene DUF1220 regions produces, can cause growth and development of brain disorders.

In researching the HYDIN2 or HYDIN - paralogy is another connection between macrocephaly and duplication, as well as between microcephaly and deletions, have been discovered. This part of the 1q21.1 is involved in the development of the brain. It is believed that there is a dose- sensitive gene. When this gene is not in the 1q21.1 region is available, it leads to microcephaly. Is a copy of the HYDIN2 HYDIN, which was found to 16q22.2.


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