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.
Additionally, we propose that centriole amplification triggered by STIL stabilization is the underlying cause of microcephaly in human patients with corresponding STIL mutations.
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.