A Novel Missense Variant in the TCOF1 Gene in one Chinese Case With Treacher Collins Syndrome.

The purpose of this study is to analyze the clinical characteristics of a Treacher Collins syndrome (TCS) patient carrying a de novo variant of TCOF1, and briefly analyze the correlation between genetic results and clinical features. Also, the pathogenesis and clinical treatment of TCS are reviewed.A Chinese pedigree with TCS containing 8 members was enrolled. Phenotype of the proband was evaluated by a surgeon, then whole exome sequencing of the proband was performed. Then we verified the proband-derived variants by Sanger sequencing in the pedigree. Correlation between genotype and phenotype was analyzed.The study was conducted in a stomatological hospital.A Chinese pedigree with TCS containing 8 members.To ascertain the genetic variants in the Chinese pedigree with TCS.Blood samples were collected.We reported a case of typical TCS with a de novo missense variant (NM_001371623.1:c.38T>G, p.(Leu13Arg)) in exon 1 of TCOF1, who presented asymmetrical facial abnormalities, including downward slanting of the palpebral fissures, sparse eyebrows, lateral tilt of the eyeballs, bilateral external ears deformities, hypoplasia of midface, reduction of the zygomatic body, bilateral orbital invagination, right external auditory canal atresia, mandibular ramus short deformity, cleft palate and the whole face was convex.This research found a novel variant of TCS in Chinese, expanding the spectrum of TCS pathogenic variants. Genetic results combined with clinical phenotype can make a definite diagnosis and provide genetic counseling for the family.

[Murine model of Graves disease induced by thyroid-stimulating hormone receptor gene transfected via liposome].

OBJECTIVE: To compare the efficacy of different expression vectors, target genes, and immunization procedures in transfecting mice via liposome to construct murine model of Graves disease. METHODS: We linked pCDNA3.1(+) and pUBC to full-length human TSHR and TSHR A subunit cDNA to yield four plasmids, which were later injected intramascularly or subcutaneously into female Balb/c mice via liposome. The blood anti-TSHR antibody (TRAb) were determined and the body weight were measured after each immunization. Serum thyroid hormone levels were measured after the animals were sacrificed. RESULTS: In mice immunized with pUBC, no significant variance with control in weight nor serum TRAb concentration was observed. Weight gain in pCDNA3.1(+) group was significantlyly slower than controls (p<0.05), and serum TRAb concentration was also significantly elevated. In pCDNA group, animals immunized with TSHR A subunit (TSHRA subgroup) as the target gene revealed even significantly slower weight gain (p<0.001) and even faster TRAb elevation than those immunized with full length TSHR. Significantly higher FT4 (p=0.023) was observed in TSHRA and TSHR subgroups, which was reversely correlated to weight gain, but no significant difference (p>0.05) in FT3 was observed. Weight gain and TRAb concentration mainly varied in the later period of immunization. CONCLUSIONS: Immunization with pCDNA3.1(+) and TSHR A subunit gene together with higher immunization frequency increases the chance of model induction. Furthermore, FT4 is a better indicator for assessing the thyroid function in this model.