15q13.3 microdeletion syndrome - Unique - The Rare Chromosome ...

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The KLF13 (Kruppel-like transcription factor 13) gene has recently been reported to be involved in cardiac development (van Bon 2009). Genes located on 15q13.3: 15q13.2 15q13.3 ARHGAP11B MRMR15 MTMR10 TRPM1 KLF13 OTUD7A CHRNA7 It is important to remember that while identifying the gene(s) responsible for certain features of 15q13.3 microdeletion syndrome is valuable and may help guide future studies, it does not lead directly to immediate improved treatment. Additionally, even if the supposedly responsible gene is missing it does not always mean that the associated feature(s) will be present. Other genetic and environmental factors often have a role in determining the presence or absence of a particular feature. How did this happen? In many cases the 15q13.3 microdeletion was inherited from a parent (Sharp 2008; Ben- Shachar 2009; Pagnamenta 2009; van Bon 2009; Le Pichon 2010; Liao 2011; Muhle 2011; Spielman 2011; Hoppman-Chaney 2012; Unique). In some cases the 15q13.3 microdeletion occurs out of the blue for no obvious reason. The genetic term for this is de novo (dn) and at first sight, both parents have normal chromosomes. De novo 15q13.3 microdeletions are caused by a mistake that is thought to occur when the parents’ sperm or egg cells are formed. At one point in the formation, all the chromosomes including the two chromosome 15s pair up and swap segments. To pair up precisely, each chromosome ‘recognises’ matching or near-matching DNA sequences on its partner chromosome. However, throughout the chromosomes there are many DNA sequences that are so similar that it is thought that mispairing can occur. Although no-one has ever seen this happen, it is believed that when the exchange of genetic material - known as ‘crossing over’ - occurs after mismatching, it is unequal, looping out and excising a length of the chromosome. What is certain is that as a parent there is nothing you could have done to prevent this from happening. No environmental, dietary or lifestyle factors are known to cause 15q13.3 microdeletions. There is nothing that either parent did before or during pregnancy that caused the microdeletion. 16
Can it happen again? Where both parents have normal chromosomes, it is unlikely that another child will be born with a 15q13.3 microdeletion or any other chromosome disorder. Where one parent has the same deletion as the child, the possibility of having another child with the deletion can be as high as 50 per cent in each pregnancy. In families where the parent appears to be unaffected but the child is affected, we cannot yet predict whether another child with the deletion would be affected by it or not. If they wish, parents should have the opportunity to meet a genetic counsellor to discuss the specific recurrence risks and options for prenatal and preimplantation genetic diagnosis (PGD). PGD requires the use of in vitro fertilisation and embryo biopsy, and only healthy embryos are transferred to the mother’s uterus. If the parents choose to conceive naturally, prenatal diagnosis options include chorionic villus sampling (CVS) and amniocentesis to test the baby’s chromosomes. Testing is generally very accurate, although not all of these tests are available in all parts of the world. Could my child with a 15q13.3 microdeletion also have children with the microdeletion? Yes, this is perfectly possible and has been seen repeatedly. The medical literature reports many parents who have passed the deletion on to their children. We have not known about the condition for long enough to be certain if it affects fertility but it is likely that fertility will be normal. In each pregnancy, someone with the deletion theoretically has a 50 per cent risk of passing it on and a 50 per cent chance of having a child without the microdeletion. Their ability to look after a child is very likely to be closely related to any learning difficulty they may have themselves. References Ben-Shachar S, Lanpher B, German JR, Qasaymeh M, Potocki L, Nagamani SC, Franco LM, Malphrus A, Bottenfield GW, Spence JE, Amato S, Rousseau JA, Moghaddam B, Skinner C, Skinner SA, Bernes S, Armstrong N, Shinawi M, Stankiewicz P, Patel A, Cheung SW, Lupski JR, Beaudet AL, Sahoo T. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J Med Genet. 2009 Jun;46(6):382-8. PMID: 19289393 Endris V, Hackmann K, Neuhann TM, Grasshoff U, Bonin M, Haug U, Hahn G, Schallner JC, Schröck E, Tinschert S, Rappold G, Moog U. Homozygous loss of CHRNA7 on chromosome 15q13.3 causes severe encephalopathy with seizures and hypotonia. Am J Med Genet A. 2010 Nov;152A(11):2908-11. doi: 10.1002/ajmg.a.33692. PMID:20979196 International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. 2008 Sep 11;455(7210):237-41. PMID: 18668038 Helbig I, Mefford HC, Sharp AJ, Guipponi M, Fichera M, Franke A, Muhle H, de Kovel C, Baker C, von Spiczak S, Kron KL, Steinich I, Kleefuss-Lie AA, Leu C, Gaus V, Schmitz B, Klein KM, Reif PS, Rosenow F, Weber Y, Lerche H, Zimprich F, Urak L, Fuchs K, Feucht M, Genton P, Thomas P, Visscher F, de Haan GJ, Møller RS, Hjalgrim H, Luciano D, Wittig M, Nothnagel M, Elger CE, Nürnberg P, Romano C, Malafosse A, Koeleman BP, Lindhout D, Stephani U, Schreiber S, Eichler EE, Sander T. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy.Nat Genet. 2009 Feb;41 (2):160-2. PMID: 19136953 Hoppman-Chaney N, Wain K, Seger P, Superneau D, Hodge J. Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes 17
Page 1 and 2: 15q13.3 microdeletion syndrome rare
Page 3 and 4: Looking at 15q13.3 You can’t see
Page 5 and 6: How common is it? It is surprisingl
Page 7 and 8: (floppiness) and weight loss. Two b
Page 9 and 10: Behaviour Some children with 15q13.
Page 11 and 12: “He has a lack of co-ordination a
Page 13 and 14: 2009; Pagnamenta 2009; van Bon 2009
Page 15: Puberty There is limited informatio
Page 19 and 20: Notes 19

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