[Clinical and genetic characteristics of 12 cases of Loeys-Dietz syndrome].

Objective: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes.
Methods: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed.
Results: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously.
Conclusion: Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.