Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings.
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...
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doaj-64dc7400317b48858eaf50a81f9601292020-11-25T01:19:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011741810.1371/journal.pone.0117418Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings.Charlotte MoudenMarie de TayracChristèle DubourgSophie RoseWilfrid CarréHouda Hamdi-RozéMarie-Claude BabronLinda AkloulBénédicte Héron-LongeSylvie OdentValérie DupéRégis GietVéronique DavidHoloprosencephaly (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.http://europepmc.org/articles/PMC4319975?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charlotte Mouden Marie de Tayrac Christèle Dubourg Sophie Rose Wilfrid Carré Houda Hamdi-Rozé Marie-Claude Babron Linda Akloul Bénédicte Héron-Longe Sylvie Odent Valérie Dupé Régis Giet Véronique David |
spellingShingle |
Charlotte Mouden Marie de Tayrac Christèle Dubourg Sophie Rose Wilfrid Carré Houda Hamdi-Rozé Marie-Claude Babron Linda Akloul Bénédicte Héron-Longe Sylvie Odent Valérie Dupé Régis Giet Véronique David Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. PLoS ONE |
author_facet |
Charlotte Mouden Marie de Tayrac Christèle Dubourg Sophie Rose Wilfrid Carré Houda Hamdi-Rozé Marie-Claude Babron Linda Akloul Bénédicte Héron-Longe Sylvie Odent Valérie Dupé Régis Giet Véronique David |
author_sort |
Charlotte Mouden |
title |
Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. |
title_short |
Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. |
title_full |
Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. |
title_fullStr |
Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. |
title_full_unstemmed |
Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. |
title_sort |
homozygous stil mutation causes holoprosencephaly and microcephaly in two siblings. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4319975?pdf=render |
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