Abstract
Many genetic and nongenetic causes for developmental delay in childhood could be identified.
Often, however, the molecular basis cannot be elucidated. As next-generation sequencing
is becoming more frequently available in a diagnostic context, an increasing number
of genetic variations are found as causative in children with developmental delay.
We performed trio exome sequencing in a girl with developmental delay and minor dysmorphological
features. Using a filter for de novo variants, the heterozygous missense variant c.812A>T,
p.(Glu217Val) was found in the candidate gene POU3F2 in our patient.
POU3F2 plays an important role in neuronal differentiation and hormonal regulation. To date,
it has not been associated with monogenic disorders. Studies on Pou3f2 knockout mice highlighted the importance of this protein in the development of the
brain. Furthermore, microdeletions with an overlapping region including only POU3F2 and FBXL4 were linked to developmental delay in six unrelated families. Therefore, POU3F2 is a strong candidate gene for developmental delay, although functional assays proving
this assumption still have to be done.
Keywords
de novo - missense - POU3F2 - developmental delay - dysmorphological - exome sequencing
