Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.
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.
Feuk
Lars
L
The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Kalervo
Aino
A
Lipsanen-Nyman
Marita
M
Skaug
Jennifer
J
Nakabayashi
Kazuhiko
K
Finucane
Brenda
B
Hartung
Danielle
D
Innes
Micheil
M
Kerem
Batsheva
B
Nowaczyk
Malgorzata J
MJ
Rivlin
Joseph
J
Roberts
Wendy
W
Senman
Lili
L
Summers
Anne
A
Szatmari
Peter
P
Wong
Virginia
V
Vincent
John B
JB
Zeesman
Susan
S
Osborne
Lucy R
LR
Cardy
Janis Oram
JO
Kere
Juha
J
Scherer
Stephen W
SW
Hannula-Jouppi
Katariina
K
D001072:Apraxias / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics; D002460:Cell Line; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D018392:Genomic Imprinting; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013577:Syndrome; D014178:Translocation, Genetic; D024182:Uniparental Disomy
C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors