Journal Article

Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans

Jung Hwa Seo, Yulia Zilber, Sima Babayeva, JiaJia Liu, Paulina Kyriakopoulos, Patrizia De Marco, Elisa Merello, Valeria Capra, Philippe Gros and Elena Torban

in Human Molecular Genetics

Volume 20, issue 22, pages 4324-4333
Published in print November 2011 | ISSN: 0964-6906
Published online August 2011 | e-ISSN: 1460-2083 | DOI:
Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans

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Neural tube defects (NTDs) are a heterogeneous group of common severe congenital anomalies which affect 1–2 infants per 1000 births. Most genetic and/or environmental factors that contribute to the pathogenesis of human NTDs are unknown. Recently, however, pathogenic mutations of VANGL1 and VANGL2 genes have been associated with some cases of human NTDs. Vangl genes encode proteins of the planar cell polarity (PCP) pathway that regulates cell behavior during early stages of neural tube formation. Homozygous disruption of PCP genes in mice results in a spectrum of NTDs, including defects that affect the entire neural axis (craniorachischisis), cranial NTDs (exencephaly) and spina bifida. In this paper, we report the dynamic expression of another PCP gene, Fuzzy, during neural tube formation in mice. We also identify non-synonymous Fuzzy amino acid substitutions in some patients with NTDs and demonstrate that several of these Fuzzy mutations affect formation of primary cilia and ciliary length or affect directional cell movement. Since Fuzzy knockout mice exhibit both NTDs and defective primary cilia and Fuzzy is expressed in the emerging neural tube, we propose that mutations in Fuzzy may account for a subset of NTDs in humans.

Journal Article.  5890 words.  Illustrated.

Subjects: Genetics and Genomics

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