title: A balanced de novo inv(7)(p14.3q22.3) disrupting PDE1C and ATXN7L1 in a 14-year old developmentally delayed boy.
abstract: We report a 14 year old male patient ascertained for developmental delay, carrying a de novo pericentric inversion on chr(7)(p14.3q22.3). Sequencing revealed that the breakpoints overlap a LTR sequence on 7q22.3 and a LINE on 7p14.3. A TTTAAA motif was found in proximity of the breakpoints on both arms. In addition the sequencing detected several small micro-rearrangements, deletion, duplication, insertion, at the breakpoints. No significant sequence identity exists between the 7p14.3 and 7q22.3 breakpoints. These features at the breakpoint junctions suggest that the inversion was triggered by the TTTAAA motif, LTR and LINE and healed by a Non Homologous End Joining (NHEJ) mechanism. The genes ATXN7L1 and PDE1C are disrupted by the inversion. PDE1C is responsible for the hydrolysis of the second messenger molecules cAMP and cGMP and is highly expressed in the human heart and certain brain regions. In mice, Pde1c is expressed in migrating neuronal cells within the central nervous system during early embryo development. Although neuronal migration disorder was not seen in our patient, this is the first patient described with haploinsufficiency of PDE1C possibly causing developmental delay.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital and University of Oslo, Norway. t.y.gamage@studmed.uio.no
authors.forename: Thilini H
authors.initials: TH
authors.lastname: Gamage
authors.forename: Doriana
authors.initials: D
authors.lastname: Misceo
authors.forename: Madeleine
authors.initials: M
authors.lastname: Fannemel
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
mesh_terms: D000293:Adolescent; D000067719:Ataxin-7; D056905:Chromosome Breakpoints; D007446:Chromosome Inversion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000235:genetics*; D059766:DNA End-Joining Repair; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020079:Terminal Repeat Sequences
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; C000593831:Atxn7 protein, mouse; D009419:Nerve Tissue Proteins; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517272:PDE1C protein, human
keywords: ATXN7L1; Developmental disorder; Inversion (7)(p14.3q22.3); NHEJ; PDE1C; TTTAAA motif