RT Journal Article
SR Electronic
T1 <em>FOXP2</em> variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 64
OP 72
DO 10.1136/jmedgenet-2016-104094
VO 54
IS 1
A1 Reuter, Miriam S
A1 Riess, Angelika
A1 Moog, Ute
A1 Briggs, Tracy A
A1 Chandler, Kate E
A1 Rauch, Anita
A1 Stampfer, Miriam
A1 Steindl, Katharina
A1 Gläser, Dieter
A1 Joset, Pascal
A1 ,
A1 Krumbiegel, Mandy
A1 Rabe, Harald
A1 Schulte-Mattler, Uta
A1 Bauer, Peter
A1 Beck-Wödl, Stefanie
A1 Kohlhase, Jürgen
A1 Reis, André
A1 Zweier, Christiane
YR 2017
UL http://jmg.bmj.com/content/54/1/64.abstract
AB Background Disruptions of the FOXP2 gene, encoding a forkhead transcription factor, are the first known monogenic cause of a speech and language disorder. So far, mainly chromosomal rearrangements such as translocations or larger deletions affecting FOXP2 have been reported. Intragenic deletions or convincingly pathogenic point mutations in FOXP2 have up to date only been reported in three families. We thus aimed at a further characterisation of the mutational and clinical spectrum.Methods Chromosomal microarray testing, trio exome sequencing, multigene panel sequencing and targeted sequencing of FOXP2 were performed in individuals with variable developmental disorders, and speech and language deficits.Results We identified four different truncating mutations, two novel missense mutations within the forkhead domain and an intragenic deletion in FOXP2 in 14 individuals from eight unrelated families. Mutations occurred de novo in four families and were inherited from an affected parent in the other four. All index patients presented with various manifestations of language and speech impairment. Apart from two individuals with normal onset of speech, age of first words was between 4 and 7 years. Articulation difficulties such as slurred speech, dyspraxia, stuttering and poor pronunciation were frequently noted. Motor development was normal or only mildly delayed. Mild cognitive impairment was reported for most individuals.Conclusions By identifying intragenic deletions or mutations in 14 individuals from eight unrelated families with variable developmental delay/cognitive impairment and speech and language deficits, we considerably broaden the mutational and clinical spectrum associated with aberrations in FOXP2.