Additionally, we propose that centriole amplification triggered by STIL stabilization is the underlying cause of microcephaly in human patients with corresponding STIL mutations.
Here we show that a homozygous truncating mutation of STIL not only causes severe autosomal recessive microcephaly, but also lobar holoprosencephaly in an extended consanguineous Pakistani family.
Exogenous re-expression of STIL or STILmicrocephaly mutants compatible with human survival, induced non-templated, de novo generation of centrioles in STIL(-/-) cells.
This case demonstrates the state-of-the-art approach to the clinical challenge of prenatal microcephaly and defines unique findings associated with compound heterozygous STIL gene mutations c.2354_2355dupGA and c.3835C>T.