The area of 1q21.1 is one of the most difficult parts of the human genome to map.Because of the repetitions in 1q21.1, there is a larger chance of an unequal crossing-over during meiosis. CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions). Typing
A common deletion is restricted to the distal area. This is a Class I-deletion.In some cases the deletion is so large that the proximal area is involved as well, the so-called Class II-deletion. There are some complex cases in which both the proximal area and the distal area are affected, while the area in between is normal. There are also some a-typical variants. Related genes
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. Diagnostics
A de novo-situation appears in about 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 a developmental disorder or another problem, and later it appeared that the parent was affected as well. In families where both parents have tested negative for the syndrome, chances of a second child with the syndrome are extremely low.
Symptoms and signs
Recognised symptoms are:
Only one set of genes on the two chromosomes function (haploinsufficiency)
Thrombocytopenia-absent radius (TAR syndrome), in case of a class II-deletion
Neurological-psychiatric problems: schizophrenia; epilepsy; learning problems; cognitive disabilities — 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 (microcephaly); prominent forehead; bulbous nose; deep-set eyes; broad thumbs; broad toes; squint; very flexible joints; clavicular pseudoarthrosis (the collarbone doesnt develop normally) (class II-deletion); an extra transverse crease of the fifth finger (class II-deletion)); problems with the development of the vagina (Müllerian aplasia)
Eyes: cataracts
Heart abnormalities and cardiovascular anomalies (30% of the cases): anomalous origin of the coronary artery (Class II-deletion)
Kidneys: missing kidney or floating kidneys
Cancer: neuroblastoma
Sleep disturbancesIt 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.A common deletion is between 1.0–1.9Mb. Mefford states that the standard for a deletion is 1.35Mb. The largest deletion seen on a living human is over 5 Mb. Cause
Meiosis is the process of dividing cells in humans. In meiosis, the chromosome pairs split and a representative of each pair goes to one daughter cell. In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after being randomized.