TAB2 deletions and variants located at chromosome 6q25.1.
Traditionally the loss of the TAB2 gene, located at 6q25.1, is linked to heart problems (cardiomyopathy and congenital heart defects). The authors report 11 previously non-described patients with deletions of 6q25 involving TAB2 and compare their manifestations to 25 patients known from the literature. Most of the newly reported patients were recruited via social media. They also studied 14 new patients with mutations in the TAB2 gene and 22 such patients from the literature. The size of the deletions among the new patients reported by the authors varied from 1.68 Mb to 14.31 Mb. In several patients with deletions TAB2 was the only deleted gene. Almost all the newly reported patients (both with deletions and mutations) had relatively short stature and revealed mild dysmorphic features (broad forehead, hypertelorism, ptosis, abnormal form and position of the ears). Heart defects were found in 31/36 patients with deletions and 31/36 patients with mutations. The incidence of cardiomyopathy was also similar in both groups (11/36 in the “deletion” group and 12/36 in the “mutation” group). Most patients in both groups showed hypermobility of the large joints. Therefore both mutations of the TAB2 and deletions 6q25.1 involving this gene show a similar clinical picture which includes growth delay, dysmorphism and connective tissue abnormalities. The authors conclude that the TAB2 gene is the main cause of this condition, and the role of TAB2 is not limited to heart pathology. The association of the above-mentioned symptoms resembles the typical phenotype of Noonan syndrome (NS) patients. When a patient is suspected of having NS, but his/her testing for mutations in the NS-common genes produce negative results, an examination of the TAB2 gene is reasonable. Developmental delay, however, was common for patients with deletions (19/36) but rare for patients with mutations (4/36). Most likely, deletions of the genes neighboring TAB2 may play a main role in producing developmental delay in these patients.
Engwerda A. et al. “TAB2 deletions and variants cause a highly recognizable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility”. “Eur. J. Hum. Genet.” 2021, v. 29 (11), 1669-1676.
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