2q33.1 microdeletion and SATB2 gene

2q33.1 microdeletion and the SATB2 gene – phenotypic effects.

Deletions of 2q33.1 involving the SATB2 gene are relatively rare. This disorder is known also as Glass syndrome. Only 33 cases of this condition have been reported previously. The authors report 17 new patients and provide a detailed analysis of all 50 patients. 23 out of 50 patients were males. The size of the deletion varied from 0.6 Mb to 26.3 Mb. Three patients had deletions larger than 15 Mb. The origin of the deletion was known in 18 cases: 17 deletions occurred “de novo” and only one case was caused by a familial rearrangement. All patients demonstrated developmental delay, the mean age of walking was 36 months. 13 out of 32 were non-verbal after 4 years of age. Patients with this condition usually have a low birth weight and height, and the difference between patients and their healthy peers becomes more significant with as patients age. 85% had different behavioral problems, including sleeping problems (50%), agitation (45%) and hyperactivity (25%). 7 out of 43 patients were autistic. Facial dysmorphism is very common (90%). 50% of patients had cleft palate. Various cardiovascular problems were reported in 11/42 patients. Morphological defects of the brain, kidneys and other internal organs (except heart) are not characteristic. A significant number of patients had deletions involving more proximal segments of 2q (2q32) with the loss of two collagen genes COL3A1 and COL5A2. 6 out of 10 such patients additionally had aortic dilation non-characteristic for patients without loss of these collagen genes. A comparison of 50 patients with deletions involving SATB2 with 152 patients having mutations in this gene showed that clinically these groups were very similar which confirms the leading role of the SATB2 in the origin of this disorder. The only significant difference involved growth retardation, which occurred in 65% patients with deletions but only in 31% of patients with mutations. Most likely, the loss of additional genes in persons with deletions may be responsible for this finding.

Zarate Y.A. et al. “Growth, development, and phenotypic spectrum of individuals with deletion of 2q33.1 involving SATB2”. “Clin. Genet.” 2021, v. 99, 547-557.