title: Comparative deletion mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability.
abstract: BACKGROUND
  While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microdeletions in the short arm have been documented. More than half of the 1p microdeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microdeletions have not been clearly defined.
  
  
  RESULTS
  We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microdeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative deletion mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microdeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly.
  
  
  CONCLUSIONS
  We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microdeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability.
authors.affiliation: Department of Obstetrics & Gynecology, Augusta University, 1120 15th Street, Augusta, GA 30912 USA ; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA.
authors.forename: Jonathan D J
authors.initials: JD
authors.lastname: Labonne
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Animal Science, Division of Applied Life Science (BK21plus), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongsangnam-do Korea.
authors.forename: Il-Keun
authors.initials: IK
authors.lastname: Kong
authors.affiliation: Department of Obstetrics & Gynecology, Augusta University, 1120 15th Street, Augusta, GA 30912 USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.affiliation: Department of Obstetrics & Gynecology, Augusta University, 1120 15th Street, Augusta, GA 30912 USA ; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA ; Neuroscience Program, Medical College of Georgia, Augusta University, Augusta, GA 30912 USA.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
authors.affiliation: Department of Obstetrics & Gynecology, Augusta University, 1120 15th Street, Augusta, GA 30912 USA ; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912 USA.
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
keywords: 1p microdeletion; Craniofacial anomalies; DAB1; DNAJC6; DOCK7; Delayed psychomotor development; HOOK1; Intellectual disability; NFIA; PDE4B