title: A patient with five chromosomal rearrangements and a 2q31.1 microdeletion.
abstract: BACKGROUND
  Complex chromosomal rearrangements and chromosomal deletion and duplication syndromes are commonly associated with abnormal clinical phenotypes. The 2q31.1 microdeletion syndrome is a rare cytogenetic event that leads to limb and multi-internal organ anomalies. In this study we investigated the genetic basis of the physical and mental symptoms exhibited by a 4-year-old boy with a suspected 2q31.1 deletion.
  
  
  METHODS
  Cytogenetic and molecular techniques including karyotyping, array-based comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH) and real-time PCR were used to identify the nature and extent of chromosome abnormalities in the patient.
  
  
  RESULTS
  A 3.6Mb interstitial microdeletion of 2q31.1 was identified in association with complex balanced genomic structural rearrangements involving chromosomes 2, 3, 6, 15 and 18. The 2q31.1 deletion resulted in the loss of one copy of several known disease genes, including GAD1, DCAF17, SLC25A12 and ITGA6 associated with mental retardation and facial abnormalities and DLX1/DLX2 partially associated with limb abnormalities. Two additional genes, HOXD13 and CHN1, required for normal limb and eye development that map immediately distal to the 2q31.1 deletion had normal copy numbers, although CHN1 was found to express at a lower level in patient's lymphocytes.
  
  
  CONCLUSIONS
  We speculated that the 2q31.1 deletion and/or translocation may have a positional effect which reduces expression of HOXD13 and CHN1 causing haplo-insufficiency, and in combination with the hemizygous expression of the disease genes at 2q31.1, provides a plausible explanation for the diverse clinical symptoms exhibited by the patient.
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Mao
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, China.
authors.forename: Min-Juan
authors.initials: MJ
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Joint Centre with Utrecht University-Genetic Core, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kwong Wai
authors.initials: KW
authors.lastname: Choy
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Li
authors.affiliation: Berry Genomics, Ltd., China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215002, China. Electronic address: cyandzh@sohu.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002675:Child, Preschool; D020848:Chimerin 1 / Q000235:genetics; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
chemical_list: D020848:Chimerin 1; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: 2q31.1 microdeletion syndrome; CHN1; Complex chromosome rearrangement; HOXD13; Translocation