ArticleMolecular genetics and metabolism2012
Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in holoprosencephaly probands to describe the parameters limiting the observed frequency of mutant gene×gene interactions.
Article in Molecular genetics and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management.Children (Basel, Switzerland) · 2023Review
- Brain Organization and Human Diseases.Cells · 2022Review
- Article
- CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy.Journal of applied genetics · 2021Article
- Δ9-Tetrahydrocannabinol inhibits Hedgehog-dependent patterning during development.Development (Cambridge, England) · 2021Article
- NewMolecular syndromology · 2021Article
- Concepts in Multifactorial Etiology of Developmental Disorders: Gene-Gene and Gene-Environment Interactions in Holoprosencephaly.Frontiers in cell and developmental biology · 2021Review
- Article
- Middle interhemispheric variant of holoprosencephaly: First prenatal report of a ZIC2 missense mutation.Clinical case reports · 2020Article
- Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Article
- Modeling the complex etiology of holoprosencephaly in mice.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Review
- Link between the causative genes of holoprosencephaly: Zic2 directly regulates Tgif1 expression.Scientific reports · 2018Article
- In-depth investigations of adolescents and adults with holoprosencephaly identify unique characteristics.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
- BOC is a modifier gene in holoprosencephaly.Human mutation · 2017Article
- Ethanol itself is a holoprosencephaly-inducing teratogen.PloS one · 2017Article
- Molecular analysis of holoprosencephaly in South America.Genetics and molecular biology · 2014Article
- FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly.Journal of medical genetics · 2013Article
- NODAL and SHH dose-dependent double inhibition promotes an HPE-like phenotype in chick embryos.Disease models & mechanisms · 2013Article
- Rescue of holoprosencephaly in fetal alcohol-exposed Cdon mutant mice by reduced gene dosage of Ptch1.PloS one · 2013Article
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Authors and funding
4 authors.
Funding
Abstract
Clinical molecular diagnostic centers routinely screen SHH, ZIC2, SIX3 and TGIF for mutations that can help to explain holoprosencephaly and related brain malformations. Here we report a prospective Sanger sequence analysis of 189 unrelated probands referred to our diagnostic lab for genetic testing. We identified 28 novel unique mutations in this group (15%) and no instances of deleterious mutations in two genes in the same subject. Our result extends that of other diagnostic centers and suggests that among the aggregate 475 prospectively sequenced holoprosencephaly probands there is negligible evidence for direct gene-gene interactions among these tested genes. We model the predictions of the observed mutation frequency in the context of the hypothesis that gene×gene interactions are a prerequisite for forebrain malformations, i.e. the "multiple-hit" hypothesis. We conclude that such a direct interaction would be expected to be rare and that more subtle genetic and environmental interactions are a better explanation for the clinically observed inter- and intra-familial variability.
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