Abstract
Mutations or deletions affecting production of the SHOX gene are responsible for a small portion of cases with isolated short stature (ISS). We were interested if SHOX gene polymorphic variants predispose for the ISS phenotype.
Our sample was made of 43 unrelated probands in charge of the Department of Biology and Medical Genetics General Teaching Hospital and 1st Faculty of Medicine, Charles University in Prague. Study inclusion criteria were the presence of short stature (-2,0 SD) in combination with at least one of following symptoms: disproportionate stature, cubitus valgus, short forearm, bowing of forearm, muscular hypertrophy, or dislocation of ulna (at elbow).
A population sample of 96 individuals was used to compare the frequencies. DNA sequencing was done of SHOX gene exons 1 (including promotor), 2, 3, 4, 5 and coding parts of exons 6a and 6b.
Overall, eleven polymorphic variants (promoter, exon 1, exon 2, and exon 6b) were detected and one unique mutation in exon 6a. Four polymorphisms were already described in the SHOX database (SHOX @ http://www.hd-lovd.uni-hd.de/).
Three promoter polymorphism and one sequence variant from the exon 1 are in a strong linkage. There was no statistically significant difference in rare allele frequencies between ISS group and population sample.
Our study indicates that SHOX gene polymorphic variants are not significantly associated with isolated short stature.