STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly

Hum Genet. 2015 Jan;134(1):45-51. doi: 10.1007/s00439-014-1487-4. Epub 2014 Sep 14.


Holoprosencephaly is a clinically and genetically heterogeneous midline brain malformation associated with neurologic manifestations including developmental delay, intellectual disability and seizures. Although mutations in the sonic hedgehog gene SHH and more than 10 other genes are known to cause holoprosencephaly, many patients remain without a molecular diagnosis. 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. STIL mutations have previously been linked to centrosomal defects in primary microcephaly at the MCPH7 locus. Our results thus expand the clinical phenotypes associated with biallellic STIL mutations to include holoprosencephaly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child, Preschool
  • Consanguinity
  • Female
  • Holoprosencephaly / genetics*
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Microcephaly / genetics*
  • Mutation / genetics*
  • Pakistan
  • Young Adult


  • Intracellular Signaling Peptides and Proteins
  • STIL protein, human

Supplementary concepts

  • Microcephaly, Primary Autosomal Recessive, 7