title: ALX4 gain-of-function mutations in nonsyndromic craniosynostosis.
abstract: Craniosynostosis is the early fusion of one or more sutures of the infant skull and is a common defect occurring in approximately 1 of every 2,500 live births. Nonsyndromic craniosynostosis (NSC) accounts for approximately 80% of all cases and is thought to have strong genetic determinants that are yet to be identified. ALX4 is a homeodomain transcription factor with known involvement in osteoblast regulation. By direct sequencing of the ALX4 coding region in sagittal or sagittal-suture-involved nonsyndromic craniosynostosis probands, we identified novel, nonsynonymous, familial variants in three of 203 individuals with NSC. Using dual-luciferase assay we show that two of these variants (V7F and K211E) confer a significant gain-of-function effect on ALX4. Our results suggest that ALX4 variants may have an impact on the genetic etiology of NSC.
authors: Section of Genetics, Department of Pediatrics, University of California-Davis, Sacramento, CA 95817, USA.
authors: Garima
authors: G
authors: Yagnik
authors: Apar
authors: A
authors: Ghuman
authors: Sundon
authors: S
authors: Kim
authors: Christina G
authors: CG
authors: Stevens
authors: Virginia
authors: V
authors: Kimonis
authors: Joan
authors: J
authors: Stoler
authors: Pedro A
authors: PA
authors: Sanchez-Lara
authors: Jonathan A
authors: JA
authors: Bernstein
authors: Cyril
authors: C
authors: Naydenov
authors: Hicham
authors: H
authors: Drissi
authors: Michael L
authors: ML
authors: Cunningham
authors: Jinoh
authors: J
authors: Kim
authors: Simeon A
authors: SA
authors: Boyadjiev
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017124:Conserved Sequence; D003398:Craniosynostoses / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C416676:ALX4 protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors