Variation in CASP10 gene is associated with idiopathic talipes equinovarus.
Idiopathic talipes equinovarus (ITEV), more commonly known as clubfoot, is a developmental deformity characterized by rigid ankle equinus, hindfoot varus, and forefoot adduction. This common birth defect is treatable, but the etiology of ITEV is largely unknown. Recently, a deletion in the chromosomal region 2q31-33 was found to be associated with clubfoot. Microsatellite markers spanning the region were genotyped in 57 multiplex ITEV families and 83 simplex trios. Family-based analysis revealed that two microsatellite markers, GATA149B10 and D2S1371, were associated with ITEV in the simplex trios. The 6cM region between the two markers contained the candidate genes CASP8, CASP10, and CFLAR. These genes encode proteins that are regulators of apoptosis, which is important during growth and development. Genotyping of SNPs throughout the genes in this sample of ITEV families has revealed positive linkage with association to the major allele of a variant in CASP10 in simplex ITEV white and Hispanic trios. This study is the first to find evidence for a candidate gene for ITEV and provides a scientific foundation to further explore the contributions of other apoptotic genes in the etiology of clubfoot.
Heck
Amy L
AL
University of Texas-Houston School of Public Health, Houston, TX 77225, USA.
Bray
Molly S
MS
Scott
Allison
A
Blanton
Susan H
SH
Hecht
Jacqueline T
JT
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D053455:Caspase 10; D053181:Caspase 8; D020169:Caspases / Q000235:genetics; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D003025:Clubfoot / Q000235:genetics*; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D047908:Intracellular Signaling Peptides and Proteins; C505530:CASP8 protein, human; D053455:Caspase 10; D053181:Caspase 8; D020169:Caspases; C506438:CASP10 protein, human