Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.
Mental retardation affects 2-3% of the population and shows a high heritability.Neurodevelopmental disorders that include pronounced impairment in language and speech skills occur less frequently. For most cases, the molecular basis of mental retardation with or without speech and language disorder is unknown due to the heterogeneity of underlying genetic factors.We have used molecular karyotyping on 1523 patients with mental retardation to detect copy number variations (CNVs) including deletions or duplications. These studies revealed three heterozygous overlapping deletions solely affecting the forkhead box P1 (FOXP1) gene. All three patients had moderate mental retardation and significant language and speech deficits. Since our results are consistent with a de novo occurrence of these deletions, we considered them as causal although we detected a single large deletion including FOXP1 and additional genes in 4104 ancestrally matched controls. These findings are of interest with regard to the structural and functional relationship between FOXP1 and FOXP2. Mutations in FOXP2 have been previously related to monogenic cases of developmental verbal dyspraxia. Both FOXP1 and FOXP2 are expressed in songbird and human brain regions that are important for the developmental processes that culminate in speech and language.
Horn
Denise
D
Institute of Medical Genetics, Charité, University Medicine of Berlin, Berlin, Germany.
Kapeller
Johannes
J
Rivera-Brugués
Núria
N
Moog
Ute
U
Lorenz-Depiereux
Bettina
B
Eck
Sebastian
S
Hempel
Maja
M
Wagenstaller
Janine
J
Gawthrope
Alex
A
Monaco
Anthony P
AP
Bonin
Michael
M
Riess
Olaf
O
Wohlleber
Eva
E
Illig
Thomas
T
Bezzina
Connie R
CR
Franke
Andre
A
Spranger
Stephanie
S
Villavicencio-Lorini
Pablo
P
Seifert
Wenke
W
Rosenfeld
Jochen
J
Klopocki
Eva
E
Rappold
Gudrun A
GA
Strom
Tim M
TM
D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D053960:DNA Breaks; D017931:DNA Primers / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007806:Language Disorders / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D013064:Speech Disorders / Q000235:genetics*
D017931:DNA Primers; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins