TY - JOUR
T1 - Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia
AU - Feuk, Lars
AU - Kalervo, Aino
AU - Lipsanen-Nyman, Marita
AU - Skaug, Jennifer
AU - Nakabayashi, Kazuhiko
AU - Finucane, Brenda
AU - Hartung, Danielle
AU - Innes, Micheil
AU - Kerem, Batsheva
AU - Nowaczyk, Małgorzata J.
AU - Rivlin, Joseph
AU - Roberts, Wendy
AU - Senman, Lili
AU - Summers, Anne
AU - Szatmari, Peter
AU - Wong, Virginia
AU - Vincent, John B.
AU - Zeesman, Susan
AU - Osborne, Lucy R.
AU - Cardy, Janis Oram
AU - Kere, Juha
AU - Scherer, Stephen W.
AU - Hannula-Jouppi, Katariina
N1 - Funding Information:
We are grateful to the families who participated in this study. This study was supported by the Academy of Finland, the Sigrid Juselius Foundation (to J.K.), the Swedish Medical Research Council (to J.K. and L.F.), and the Genome Canada/Ontario Genomics Institute and the Hospital for Sick Children Foundation (to S.W.S.). S.W.S. is an investigator of the Canadian Institutes of Health Research and an International Scholar of the Howard Hughes Medical Institute.
PY - 2006/11
Y1 - 2006/11
N2 - Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described. We characterize 13 patients with DVD-5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available showed absence of a paternal copy of FOXP2. Five other individuals with deletions of paternally inherited FOXP2 but with incomplete clinical information or phenotypes too complex to properly assess are also described. Four of the patients with DVD also meet criteria for autism spectrum disorder. Individuals with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction, we show the maternally inherited FOXP2 to be comparatively underexpressed. Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.
AB - Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described. We characterize 13 patients with DVD-5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available showed absence of a paternal copy of FOXP2. Five other individuals with deletions of paternally inherited FOXP2 but with incomplete clinical information or phenotypes too complex to properly assess are also described. Four of the patients with DVD also meet criteria for autism spectrum disorder. Individuals with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction, we show the maternally inherited FOXP2 to be comparatively underexpressed. Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.
UR - http://www.scopus.com/inward/record.url?scp=33751113031&partnerID=8YFLogxK
U2 - 10.1086/508902
DO - 10.1086/508902
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C2 - 17033973
AN - SCOPUS:33751113031
SN - 0002-9297
VL - 79
SP - 965
EP - 972
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -