Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome

作者：Breckpot Jeroen; Budts Werner; De Zegher Francis; Vermeesch Joris R; Devriendt Koenraad^*

来源：European Journal of Medical Genetics, 2010, 53(6): 408-410.

DOI：10.1016/j.ejmg.2010.08.004

• TGFBR1
• Loeys-Dietz syndrome
• Array CGH
• Bifid uvula
• 9q duplication
• 22q13 deletion

Loeys-Dietz syndrome (LDS; OMIM:609192) is an autosomal dominant disorder characterized by hypertelorism, bifid uvula or cleft palate, and arterial tortuosity with widespread vascular aneurysms and a high risk of aortic dissection at an early age. LDS results from mutations in the transforming growth factor beta-receptor I and II (TGFBR1 and TGFBR2) genes, altering the transmission of the subcellular TGF-beta signal, mediated by increased activation of Smad2.
We report on a 17-year-old boy with pubertas tarda, a bifid uvula, camptodactyly and facial dysmorphic features, suggestive of LDS. Mutation analysis of TGFBR1 and TGFBR2 was normal. By means of molecular karyotyping two previously unreported chromosomal imbalances were detected: a 120 kb deletion on chromosome 22q13.31q13.32, inherited from an unaffected parent, and a de novo 14.6 Mb duplication on chromosome 9q22.32q31.3, comprising TGFBR1. We hypothesize that copy number gain of TGFBR1 contributes to the phenotype.

• 出版日期2010-12