title: STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly.
abstract: 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.
authors.affiliation: Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Naseebullah
authors.initials: N
authors.lastname: Kakar
authors.forename: Jamil
authors.initials: J
authors.lastname: Ahmad
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Morris-Rosendahl
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Katrin
authors.initials: K
authors.lastname: Friedrich
authors.forename: Gotthold
authors.initials: G
authors.lastname: Barbi
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Christian
authors.initials: C
authors.lastname: Kubisch
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Guntram
authors.initials: G
authors.lastname: Borck
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D016142:Holoprosencephaly / Q000235:genetics*; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C071236:STIL protein, human