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Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability


Heterozygous disruptions in FOXP1 are responsible for developmental delay, intellectual disability and speech deficit. Heterozygous germline PTCH1 disease-causing variants cause Gorlin syndrome. We describe a girl with extreme megalencephaly, developmental delay and severe intellectual disability. Dysmorphic features included prominent forehead, frontal hair upsweep, flat, wide nasal bridge, low-set, abnormally modelled ears and post-axial cutaneous appendages on the hands. Brain MRI showed partial agenesis of the corpus callosum and widely separated leaves of the septum pellucidum. Exome sequencing of a gene set representing a total of 4813 genes with known relationships to human diseases revealed an already known heterozygous de novo nonsense disease-causing variant in FOXP1 (c.1573C>T, p.Arg525Ter) and a heterozygous novel de novo frameshift nonsense variant in PTCH1 (c.2834delGinsAGATGTTGTGGACCC, p.Arg945GlnfsTer22). The composite phenotype of the patient seems to be the result of two monogenic diseases, although more severe than described in conditions due to disease-causing variants in either gene.

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We thank the members of the patient’s family for their cooperation.



This study was supported by the GINOP-2.3.2-15-2 grant (to TK and ZM) provided by the National Research, Development and Innovation Office (Hungary).

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Corresponding author

Correspondence to László Sztriha.

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Ethical approval

Written informed parental consent has been obtained. The study was approved by the Human Investigation Review Board at Albert Szent-Györgyi Clinical Centre, University of Szeged, Hungary.

Conflict of interest

The authors declare that they have no conflict of interest.

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Zombor, M., Kalmár, T., Maróti, Z. et al. Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability. J Hum Genet 63, 1189–1193 (2018).

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