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Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings.

ABSTRACT: Holoprosencephaly (HPE) is a frequent congenital malformation of the brain characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been identified in HPE patients that account for only 30% of HPE cases, suggesting the existence of other HPE genes. Data from homozygosity mapping and whole-exome sequencing in a consanguineous Turkish family were combined to identify a homozygous missense mutation (c.2150G>A; p.Gly717Glu) in STIL, common to the two affected children. STIL has a role in centriole formation and has previously been described in rare cases of microcephaly. Rescue experiments in U2OS cells showed that the STIL p.Gly717Glu mutation was not able to fully restore the centriole duplication failure following depletion of endogenous STIL protein indicating the deleterious role of the mutation. In situ hybridization experiments using chick embryos demonstrated that expression of Stil was in accordance with a function during early patterning of the forebrain. It is only the second time that a STIL homozygous mutation causing a recessive form of HPE was reported. This result also supports the genetic heterogeneity of HPE and increases the panel of genes to be tested for HPE diagnosis.

SUBMITTER: Mouden C

PROVIDER: S-EPMC4319975 | biostudies-literature |

REPOSITORIES: biostudies-literature

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A Homozygous Nonsense Thyroid Peroxidase Mutation (R540X) Consistently Causes Congenital Hypothyroidism in Two Siblings Born to a Consanguineous Family.

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Homozygous mutation in <i>MCM7</i> causes autosomal recessive primary microcephaly and intellectual disability.

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Recurrent partial rhombencephalosynapsis and holoprosencephaly in siblings with a mutation of ZIC2.

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A Novel Homozygous WDR72 Mutation in Two Siblings with Amelogenesis Imperfecta and Mild Short Stature.

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Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase Synthetase Deficiency Caused by a Homozygous L216R Mutation.

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