17q21.31 microdeletion syndrome
|17q21.31 microdeletion syndrome (Koolen De Vries Syndrome)|
|Classification and external resources|
17q21.31 microdeletion syndrome (Koolen De Vries syndrome) is a rare genetic disorder caused by a deletion of a segment of chromosome 17 which contains six genes. This deletion syndrome was discovered independently in 2006 by three different research groups.
The symptoms associated with this syndrome are variable, but common features include: low birthweight, low muscle tone at birth, poor feeding in infancy (often requiring feeding by tube for a period) and oromotor dyspraxia together with moderate developmental delays and learning disabilities but amiable behaviour. Other clinically important features include epilepsy, heart defects (atrial septal defect, ventricular septal defect) and kidney/urological anomalies. Silvery depigmentation of strands of hair have been noted in several patients. With age there is an apparent coarsening of facial features. 17q21.3 was reported simultaneously in 2006 by three independent groups, with each group reporting several patients, and is now recognised to be one of the more common recurrent microdeletion syndromes. Recently a patient with a small duplication in same segment of DNA has been described. An overview of the clinical features of the syndrome, by reviewing 22 individuals with a 17q21.31 microdeletion, estimated the disorder is present in one in every 16,000 people.
Origin and Size of Deletion
The recurrent deletion is between 500-650 kilobases (Kb) in size encompassing at least six genes, among them the microtubule-associated protein tau (MAPT). A review of five patients found the parental chromosome from which the deletion originated carried a common 900kb inversion polymorphism. The orientation of low copy repeats flanking the deleted segment, suggests the inversion in the parental chromosome influences the deletion in the child's chromosome via a non-allelic homologous recombination (NAHR) mechanism.
The deletion that causes this disease can remove up to six different genes. These include:
- The uncharacterised protein C17orf69 (also known as FLJ25168).
- Corticotropin releasing hormone receptor 1 (CRHR1, also known as CRF-R, CRF1)
- Microtubule-associated protein tau (MAPT)
- The uncharacterised protein KIAA1267 (also known as DKFZP727C091)
- Sharp AJ, Hansen S, Selzer RR, et al. (September 2006). "Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome". Nat. Genet. 38 (9): 1038–42. doi:10.1038/ng1862. PMID 16906162.
- Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos AC, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP (2006). "Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability.". Nat Genet 38 (9): 1032–7. doi:10.1038/ng1858. PMID 16906163.
- Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, Kooy RF, Reyniers E, Romano C, Fichera M, Schinzel A, Baumer A, Anderlid BM, Schoumans J, Knoers NV, van Kessel AG, Sistermans EA, Veltman JA, Brunner HG, de Vries BB (2006). "A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism.". Nat Genet 38 (9): 999–1001. doi:10.1038/ng1853. PMID 16906164.
- Lupski JR (2006). "Genome structural variation and sporadic disease traits.". Nat Genet 38 (9): 974–6. doi:10.1038/ng0906-974. PMID 16941003.
- Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, Saugier-Veber P, Pfundt R, Vissers LE, Destrée A, Grisart B, Rooms L, Van der Aa N, Field M, Hackett A, Bell K, Nowaczyk MJ, Mancini GM, Poddighe PJ, Schwartz CE, Rossi E, De Gregori M, Antonacci-Fulton LL, McLellan MD, Garrett JM, Wiechert MA, Miner TL, Crosby S, Ciccone R, Willatt L, Rauch A, Zenker M, Aradhya S, Manning MA, Strom TM, Wagenstaller J, Krepischi-Santos AC, Vianna-Morgante AM, Rosenberg C, Price SM, Stewart H, Shaw-Smith C, Brunner HG, Wilkie AO, Veltman JA, Zuffardi O, Eichler EE, de Vries BB (2008). "Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.". J Med Genet 45 (11): 710–20. doi:10.1136/jmg.2008.058701. PMID 18628315.
- Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S, Kirk EP, Love D, Ronan A, Darmanian A, Slavotinek A, Hogue J, Moeschler JB, Ozmore J, Widmer R, Bruno D, Savarirayan R, Peters G (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome.". J Med Genet 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831.
- Varela MC, Krepischi-Santos AC, Paz JA, Knijnenburg J, Szuhai K, Rosenberg C, Koiffmann CP (2006). "A 17q21.31 microdeletion encompassing the MAPT gene in a mentally impaired patient.". Cytogenet Genome Res 114 (1): 89–92. doi:10.1159/000091934. PMID 16717456.
- Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW, Cardone MF, Graves TA, Kidd JM, Cheng Z, Abouelleil A, Chen L, Wallis J, Glasscock J, Wilson RK, Reily AD, Duckworth J, Ventura M, Hardy J, Warren WC, Eichler EE (2008). "Evolutionary toggling of the MAPT 17q21.31 inversion region.". Nat Genet 40 (9): 1076–83. doi:10.1038/ng.193. PMC 2684794. PMID 19165922.
- Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E, Tolmie J, Jackson AP (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype.". Cytogenet Genome Res 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647.
- Kirchhoff M, Bisgaard AM, Duno M, Hansen FJ, Schwartz M (2007). "A 17q21.31 microduplication, reciprocal to the newly described 17q21.31 microdeletion, in a girl with severe psychomotor developmental delay and dysmorphic craniofacial features". Eur J Med Genet 50 (4): 256–63. doi:10.1016/j.ejmg.2007.05.001. PMID 17576104.
- Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S et al. (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome.". J Med Genet 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831.
- Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E et al. (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype.". Cytogenet Genome Res 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647.
- Wright EB, Donnai D, Johnson D, Clayton-Smith J (2011). "Cutaneous features in 17q21.31 deletion syndrome: a differential diagnosis for cardio-facio-cutaneous syndrome.". Clin Dysmorphol 20 (1): 15–20. doi:10.1097/MCD.0b013e32833e8f1e. PMC 3000393. PMID 21084979.
- Rao PN, Li W, Vissers LE, Veltman JA, Ophoff RA (2010). "Recurrent inversion events at 17q21.31 microdeletion locus are linked to the MAPT H2 haplotype.". Cytogenet Genome Res 129 (4): 275–9. doi:10.1159/000315901. PMID 20606400.
- 17q21.31 Research project http://www.17q21.com
- DECIPHER database entry for 17q21.31 microdeletion syndrome
- Orphanet entry for 17q21.31 microdeletion syndrome
- 17q21.31 microdeletion information leaflet for families from Unique — the rare chromosome disorder support group.