Analysis of the CHN1 gene in patients with various types of congenital ocular motility disorders

In the families of our index patients with DRS, other family members displayed DRS, see-saw nystagmus, infantile esotropia, microtropia, or Brown syndrome, respectively. In the families of our patients with cases of Brown syndrome, bilateral abduction deficiency, infantile esotropia, and unspecified strabismus occurred. The patients with congenital disorders of the oblique muscles and with congenital elevation deficiencies other than Brown syndrome had relatives with ptosis, infantile esotropia, DRS, congenital abduction deficiency, and unspecified forms of strabismus. Thus a considerable intrafamilial overlap between different types of congenital forms of motility disorders and strabismus does exist. No mutations were detected in the CHN1 gene in our patients. In addition to known polymorphisms, we identified four novel heterozygous single-nucleotide substitutions, one in the 5′UTR, two in intronic regions, and one in the coding region leading to a synonymous amino acid substitution.

We found no evidence for a causative involvement of CHN1 mutations in congenital ocular motor anomalies different from autosomal dominant Duane’s retraction syndrome and provide further evidence for genetic heterogeneity in familial forms of DRS.