Abstract:
: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.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Zombor M,Kalmár T,Maróti Z,Zimmermann A,Máté A,Bereczki C,Sztriha Ldoi
10.1038/s10038-018-0508-xsubject
Has Abstractpub_date
2018-11-01 00:00:00pages
1189-1193issue
11eissn
1434-5161issn
1435-232Xpii
10.1038/s10038-018-0508-xjournal_volume
63pub_type
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