@article {310232, title = {Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes.}, journal = {N Engl J Med}, volume = {359}, year = {2008}, month = {2008 Oct 16}, pages = {1685-99}, abstract = {

BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients.

METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons.

RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies.

CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.

}, keywords = {Autistic Disorder, Cataract, Child, Chromosome Aberrations, Chromosome Deletion, Chromosomes, Human, Pair 1, Congenital Abnormalities, Female, Gene Duplication, Gene Rearrangement, Genetic Variation, Heart Defects, Congenital, Humans, Intellectual Disability, Male, Microcephaly, Phenotype, Recombination, Genetic}, issn = {1533-4406}, doi = {10.1056/NEJMoa0805384}, author = {Mefford, Heather C and Sharp, Andrew J and Baker, Carl and Itsara, Andy and Jiang, Zhaoshi and Buysse, Karen and Huang, Shuwen and Maloney, Viv K and Crolla, John A and Baralle, Diana and Collins, Amanda and Mercer, Catherine and Norga, Koen and de Ravel, Thomy and Devriendt, Koen and Bongers, Ernie M H F and de Leeuw, Nicole and Reardon, William and Gimelli, Stefania and Bena, Frederique and Hennekam, Raoul C and Male, Alison and Gaunt, Lorraine and Clayton-Smith, Jill and Simonic, Ingrid and Park, Soo Mi and Mehta, Sarju G and Nik-Zainal, Serena and Woods, C Geoffrey and Firth, Helen V and Parkin, Georgina and Fichera, Marco and Reitano, Santina and Lo Giudice, Mariangela and Li, Kelly E and Casuga, Iris and Broomer, Adam and Conrad, Bernard and Schwerzmann, Markus and R{\"a}ber, Lorenz and Gallati, Sabina and Striano, Pasquale and Coppola, Antonietta and Tolmie, John L and Tobias, Edward S and Lilley, Chris and Armengol, Lluis and Spysschaert, Yves and Verloo, Patrick and De Coene, Anja and Goossens, Linde and Mortier, Geert and Speleman, Frank and van Binsbergen, Ellen and Nelen, Marcel R and Hochstenbach, Ron and Poot, Martin and Gallagher, Louise and Gill, Michael and McClellan, Jon and King, Mary-Claire and Regan, Regina and Skinner, Cindy and Stevenson, Roger E and Antonarakis, Stylianos E and Chen, Caifu and Estivill, Xavier and Menten, Bj{\"o}rn and Gimelli, Giorgio and Gribble, Susan and Schwartz, Stuart and Sutcliffe, James S and Walsh, Tom and Knight, Samantha J L and Sebat, Jonathan and Romano, Corrado and Schwartz, Charles E and Veltman, Joris A and de Vries, Bert B A and Vermeesch, Joris R and Barber, John C K and Willatt, Lionel and Tassabehji, May and Eichler, Evan E} }