Identification of TGFBR1 Gene Variants in Two Chinese Pedigrees with Loeys-Dietz Syndrome

To investigate a precise treatment and related gene variants in some Loeys-Dietz syndrome (LDS) patients with vascular disease.

Two probands (JX001-II1 and JX002-II1) diagnosed with LDS and their families were recruited. Routine blood test, antiphospholipid antibodies, immune globulins, nuclear antibodies (ANAs) and biochemical tests, and computed tomography angiography (CTA) were performed for probands. Deoxyribonucleic acid was collected from the two families and was sequenced by the next-generation sequencing employing the Ion Torrent platform (Life Technologies); the variants were confirmed by Sanger sequencing.

Two probands' antiphospholipid antibodies, immune globulins, and ANAs were near normal. CTA showed that both probands had an LDS patient typical arterial change: aortic aneurysm. Genetic testing of the 10 LDS-associated genes in the two probands showed that c.605C>T (JX001-II1) and c.679G>A (JX002-II1) variants were both positioned in exon 1 of TGFBR1 and it results in the substitution of highly conserved 202 alanine (Ala) for valine (Val) ( P. Ala 202Val, JX001-II1) and 227 glutamic acids (Glu) for lysine (Lys) ( P. Glu 227Lys, JX002-II1). However, the parents of both patients did not have similar symptoms and did not carry such gene variants. Proband 1 (JX001-II1) died unexpectedly during the operation preparations, whereas proband 2 (JX002-II1) underwent two operations, and the patient is currently in excellent health.

The two TGFBR1 gene variants may be a primary genetic cause of LDS. The results expand the TGFBR1 variant spectrum. Endovascular surgery can be a feasible option for LDS patients.