ALX4 gain-of-function mutations in nonsyndromic craniosynostosis

Garima Yagnik; Apar Ghuman; Sundon Kim; Christina G. Stevens; Virginia Kimonis; Joan Stoler; Pedro A. Sanchez-Lara; Jonathan A. Bernstein; Cyril Naydenov; Hicham Drissi; Michael L. Cunningham; Jinoh Kim; Simeon Boyd

doi:10.1002/humu.22166

ALX4 gain-of-function mutations in nonsyndromic craniosynostosis

Garima Yagnik, Apar Ghuman, Sundon Kim, Christina G. Stevens, Virginia Kimonis, Joan Stoler, Pedro A. Sanchez-Lara, Jonathan A. Bernstein, Cyril Naydenov, Hicham Drissi, Michael L. Cunningham, Jinoh Kim, Simeon Boyd

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1626-1629
Number of pages	4
Journal	Human Mutation
Volume	33
Issue number	12
DOIs	https://doi.org/10.1002/humu.22166
State	Published - Dec 2012

Keywords

ALX4
Craniosynostosis
Dual luciferase
Gain-of-function
Sagittal

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1002/humu.22166

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ALX4 gain-of-function mutations in nonsyndromic craniosynostosis. / Yagnik, Garima; Ghuman, Apar; Kim, Sundon; Stevens, Christina G.; Kimonis, Virginia; Stoler, Joan; Sanchez-Lara, Pedro A.; Bernstein, Jonathan A.; Naydenov, Cyril; Drissi, Hicham; Cunningham, Michael L.; Kim, Jinoh; Boyd, Simeon.

In: Human Mutation, Vol. 33, No. 12, 12.2012, p. 1626-1629.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Stoler, Joan

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AU - Kim, Jinoh

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AB - 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.

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ALX4 gain-of-function mutations in nonsyndromic craniosynostosis

Abstract

Keywords

ASJC Scopus subject areas

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