Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability

• Published in: Nature genetics Vol. 38; no. 9; pp. 1032 - 1037
• Main Authors: Gribble, Susan, Rosenberg, Carla, de Silva, Rohan, Kalaitzopoulos, Dimitrios, Cumming, Sally, Dunn, Carolyn, Rickman, Lisa, Lees, Andrew J, Prigmore, Elena, Porter, Keith, Koiffmann, Celia P, Carter, Nigel P, Shaw-Smith, Charles, Martin, Howard, Curley, Rebecca, Willatt, Lionel, Krepischi-Santos, Ana C V, Pittman, Alan M, Varela, Monica C, Firth, Helen V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.09.2006
• Subjects: Adolescent; Adult; Biological and medical sciences; Child, Preschool; Chromosome Deletion; Chromosome Inversion; Chromosomes; Chromosomes, Human, Pair 17; Developmental Disabilities - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Genomics; Haplotypes; Heterozygote; Humans; Hybridization; In Situ Hybridization, Fluorescence; Intellectual disabilities; Learning disabilities; Learning Disabilities - genetics; Male; Neuropsychology; Nucleic Acid Hybridization; Physical Chromosome Mapping; Polymorphism, Single Nucleotide; Repetitive Sequences, Nucleic Acid; tau Proteins - genetics; Learning disability; Chromosome; Developmental disorder
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1858

Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.