17q11.2 microduplication syndrome is a recently described relatively rare condition associated with a nonspecific phenotype. Intellectual disability, developmental delay, and dysmorphisms are the only clinical features common to a majority of cases. Seventeen patients have been reported so far. Here, we present another patient with 17q11.2 duplication and no signs of neurofibromatosis type 1, identified by array-CGH. We compared clinical features and genetic data with those of previously reported patients with 17q11.2 microduplications. We also analyzed the gene content of the duplicated region in order to investigate the possible role of specific genes in the clinical phenotype of our patient.

1.
Bengesser K, Cooper DN, Steinmann K, Kluwe L, Chuzhanova NA, et al: A novel third type of recurrent NF1 microdeletion mediated by nonallelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2. Hum Mutat 31:742-751 (2010).
2.
Coe BP, Witherspoon K, Rosenfeld JA, van Bon BW, Vulto-van Silfhout AT, et al: Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet 46:1063-1071 (2014).
3.
Conrad B, Antonarakis SE: Gene duplication: a drive for phenotypic diversity and cause of human disease. Annu Rev Genomics Hum Genet 8:17-35 (2007).
4.
Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, et al: A copy number variation morbidity map of developmental delay. Nat Ge- net 43:838-846 (2011).
5.
Dorschner MO, Sybert VP, Weaver M, Pletcher BA, Stephens K: NF1 microdeletion breakpoints are clustered at flanking repetitive sequences. Hum Mol Genet 9:35-46 (2000).
6.
Douglas J, Cilliers D, Coleman K, Tatton-Brown K, Barker K, et al: Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth. Nat Genet 39:963-965 (2007).
7.
Grisart B, Rack K, Vidrequin S, Hilbert P, Deltenre P, et al: NF1 microduplication first clinical report: association with mild mental retardation, early onset of baldness and dental enamel hypoplasia? Eur J Hum Genet 16:305-311 (2008).
8.
Jenne DE, Tinschert S, Reimann H, Lasinger W, Thiel G, et al: Molecular characterization and gene content of breakpoint boundaries in patients with neurofibromatosis type 1 with 17q11.2 microdeletions. Am J Hum Genet 69:516-527 (2001).
9.
Kehrer-Sawatzki H, Kluwe L, Sandig C, Kohn M, Wimmer K, et al: High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene. Am J Hum Genet 75:410-423 (2004).
10.
Kehrer-Sawatzki H, Bengesser K, Callens T, Mikhail F, Fu C, et al: Identification of large NF1 duplications reciprocal to NAHR-mediated type-1 NF1 deletions. Hum Mutat 35:1469-1475 (2014).
11.
Kehrer-Sawatzki H, Mautner VF, Cooper DN: Emerging genotype-phenotype relationships in patients with large NF1 deletions. Hum Genet 136:349-376 (2017).
12.
López Correa C, Brems H, Lázaro C, Marynen P, Legius E: Unequal meiotic crossover: a frequent cause of NF1 microdeletions. Am J Hum Genet 66:1969-1974 (2000).
13.
Lu X, Shaw CA, Patel A, Li J, Cooper ML, et al: Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. PLoS One 2:e327 (2007).
14.
Lupiáñez DG, Spielmann M, Mundlos S: Breaking TADs: how alterations of chromatin domains result in disease. Trends Genet 32:225-237 (2016).
15.
Lupski JR: Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet 14:417-422 (1998).
16.
Moles KJ, Gowans GC, Gedela S, Beversdorf D, Yu A, et al: NF1 microduplications: identification of seven nonrelated individuals provides further characterization of the phenotype. Genet Med 14:508-514 (2012).
17.
Pasmant E, Sabbagh A, Spurlock G, Laurendeau I, Grillo E, et al: NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype. Hum Mutat 31:E1506-1518 (2010).
18.
Roehl AC, Cooper DN, Kluwe L, Helbrich A, Wimmer K, et al: Extended runs of homozygosity at 17q11.2: an association with type-2 NF1 deletions? Hum Mutat 31:325-334 (2010).
19.
Shaikh TH, Gai X, Perin JC, Glessner JT, Xie H, et al: High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications. Genome Res 19:1682-1690 (2009).
20.
Spiegel M, Oexle K, Horn D, Windt E, Buske A, et al: Childhood overgrowth in patients with common NF1 microdeletions. Eur J Hum Genet 13:883-888 (2005).
21.
Steinmann K, Cooper DN, Kluwe L, Chuzhanova NA, Senger C, et al: Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination. Am J Hum Genet 81:1201-1220 (2007).
22.
Venturin M, Guarnieri P, Natacci F, Stabile M, Tenconi R, et al: Mental retardation and cardiovascular malformations in NF1 microdeleted patients point to candidate genes in 17q11.2. J Med Genet 41:35-41 (2004).
23.
Venturin M, Moncini S, Villa V, Russo S, Bonati MT, et al: Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation. Neurogenetics 7:59-66 (2006).
24.
Wang KC, Koprivica V, Kim JA, Sivasankaran R, Guo Y, et al: Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417:941-944 (2002).
25.
Weise A, Mrasek K, Klein E, Mulatinho M, Llerena JC Jr, et al: Microdeletion and microduplication syndromes. J Histochem Cytochem 60:346-358 (2012).
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