Abstract
Purpose: :
SALL genes encode putative zinc finger transcription factors and play crucial roles in human malformation syndromes. Mutations in SALL4, one of the SALL genes, have been found in patients with Duane radial ray syndrome (Okihiro syndrome) which has the combined phenotypes of Duane retraction syndrome and upper limb radial abnormalities. In this study, we searched for SALL4 gene polymorphisms in patients with Duane syndrome.
Methods: :
Six Japanese patients with Duane syndrome and 20 normal Japanese subjects participated in this study. All the patients were boys and the age ranged from 1 to 12 (mean, 4.5) years at the tme of venopuncture. Four patients showed abduction restriction and retraction in adduction in the left eye and two showed the symptoms in the right eye. Two patients had family history of strabismus: one patient had the mother with esotropia and maternal grandfather with Duane syndrome while another patient had an aunt with esotropia. At the primary gaze position, one patient showed no deviation and had no surgery, one patient showed exodeviation and underwent recession of the lateral rectus muscle of the affected eye, and the remaining four patients showed esodeviation and underwent recession of the medial rectus muscle of the affected eye. After obtaining informed consent from the parent of each patient according to the procedure approved by the institutional review board, 10 mL peripheral blood was drawn and leukocytes were isolated by gradient centrifugation. Genomic DNA was purified by phenol/chloroform extraction and ethanol precipitation. Seven DNA fragments, one covering exon 1, four covering exon 2, one covering exon 3, and one covering exon 4, were generated by polymerase chain reaction (PCR) amplification and were directly sequenced.
Results: :
The exon 2 had 4 types of single nucleotide polymorphisms while exons 1, 3, and 4 had no polymorphism. The 2104 C to C/T was found in 2 of 6 Duane patients and in 2 of 20 normal subjects (P=0.5492, Fisher exact probability test). The combination of 1927 A to A/G and 1587 T to T/G was found in 5 of 6 Duane patients and in 13 of 20 normal subjects (P=0.6279). The 1123 G to G/A was found in 2 of 6 Duane patients and 6 of 20 normal subjects (P>0.9999). The combined presence of all 4 polymorphisms was found in 2 of 6 Duane syndrome and none of 20 normal subjects (P=0.0462).
Conclusions: :
The polymorphisms of the SALL 4 gene might be a genetic risk factor for the development of Duane syndrome in the Japanese population.
Keywords: genetics • mutations • strabismus: etiology