Functional characterization of rare FOXP2 variants in neurodevelopmental disorder

Table 1 Rare FOXP2 variants in individuals with neurodevelopmental disorders

Variant description^a	Frequency in ExAC^b	Phenotype and inheritance pattern	Role in disorder^c	Reference
p.Q17L (missense) c.50A > T chr7:114426561A > T rs201649896	56/120570 (1 homozygote)	Found in a proband with CAS but not in an affected sibling. Parental genotypes not determined	Probably incidental	MacDermot et al. [8]
p.M406T (missense) c.1217 T > C chr7:114653960 T > C no rs ID	Not observed	Found in a proband with rolandic epilepsy and polymicrogyria, in two unaffected siblings and in unaffected father	Uncertain significance	Roll et al. [15]
p.P416T (missense) c.1246C > A chr7:114653989C > A rs369313543	1/121328	Present in two siblings with severe stuttering. Absent in affected father. Inherited from mother, who does not stutter but has oral motor impairments	Probably incidental	Turner et al. [9]
p.R553H (missense) c.1658G > A chr7:114662075G > A rs121908377	Not observed	Segregates with CAS in three generations of the KE family	Causal	Lai et al. [4]
p.N597H (missense) c.1789A > C chr7:114663469A > C no rs ID	1/120986	Found in a proband with CAS. Parental genotypes not determined	Uncertain significance	Laffin et al. [7]
p.R328* (stop-gain) c.982C > T chr7:114642616C > T rs121908378	Not observed	Present in a proband with CAS and in affected sibling. Inherited from affected mother	Causal	MacDermot et al. [8]
p.Q390Vfs*7 (frameshift) c.1168_1169del chr7:114652276_ 114652277del no rs ID	Not observed	De novo variant in a proband with sporadic CAS, dysarthria, and fine motor apraxia	Causal	Turner et al. [9]

^aVariants are described in accordance with Human Genome Variation Society recommendations (www.hgvs.org/mutnomen, accessed June 2016) with reference to the major transcript NM_014491.3 (ENST00000350908). Genomic coordinates refer to the hg38 assembly. The rs ID number is provided for variants that are present in dbSNP
^bVariant allele frequency in the Exome Aggregation Consortium (ExAC) dataset (http://exac.broadinstitute.org, accessed June 2016)
^cVariants are described as causal if they segregate perfectly with childhood apraxia of speech (CAS) affection status, or if they occurred de novo in sporadic cases, and if they additionally have been demonstrated to cause loss of protein function, or are very likely to do so because of protein truncation. Variants are described as probably incidental if they do not segregate with CAS and are observed in the Exome Aggregation Consortium (ExAC) dataset. Other variants are described as of uncertain significance
Note: This table does not include newly described variants that were reported by Reuter et al. [58] after the completion of the present study

ISSN: 1866-1955