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

## TL;DR

This study identifies two new TGFBR1 gene variants in Chinese families with Loeys-Dietz Syndrome, a genetic disorder affecting blood vessels.

## Contribution

The study reports novel TGFBR1 gene variants in LDS patients and highlights the potential of endovascular surgery as a treatment option.

## Key findings

- Two novel TGFBR1 gene variants (c.605C>T and c.679G>A) were identified in two LDS patients.
- Endovascular surgery was found to be a feasible treatment for LDS patients.
- The variants were not present in the parents, suggesting de novo mutations.

## Abstract

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.