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)

Access to Document

10.1002/humu.22166

Fingerprint Dive into the research topics of 'ALX4 gain-of-function mutations in nonsyndromic craniosynostosis'. Together they form a unique fingerprint.

Cite this

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

@article{b6983574930740509ecc5505733105f7,

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.",

keywords = "ALX4, Craniosynostosis, Dual luciferase, Gain-of-function, Sagittal",

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

year = "2012",

month = dec,

doi = "10.1002/humu.22166",

language = "English (US)",

volume = "33",

pages = "1626--1629",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "Wiley-Liss Inc.",

number = "12",

}

TY - JOUR

T1 - ALX4 gain-of-function mutations in nonsyndromic craniosynostosis

AU - Yagnik, Garima

AU - Ghuman, Apar

AU - Kim, Sundon

AU - Stevens, Christina G.

AU - Kimonis, Virginia

AU - Stoler, Joan

AU - Sanchez-Lara, Pedro A.

AU - Bernstein, Jonathan A.

AU - Naydenov, Cyril

AU - Drissi, Hicham

AU - Cunningham, Michael L.

AU - Kim, Jinoh

AU - Boyd, Simeon

PY - 2012/12

Y1 - 2012/12

N2 - 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.

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.

KW - ALX4

KW - Craniosynostosis

KW - Dual luciferase

KW - Gain-of-function

KW - Sagittal

UR - http://www.scopus.com/inward/record.url?scp=84869083654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869083654&partnerID=8YFLogxK

U2 - 10.1002/humu.22166

DO - 10.1002/humu.22166

M3 - Article

C2 - 22829454

AN - SCOPUS:84869083654

VL - 33

SP - 1626

EP - 1629

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 12

ER -

ALX4 gain-of-function mutations in nonsyndromic craniosynostosis

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this