Mutation screening of Chinese Treacher Collins syndrome patients identified novel TCOF1 mutations.

Treacher Collins syndrome (TCS) (OMIM 154500) is a rare congenital craniofacial disorder with an autosomal dominant manner of inheritance in most cases. To date, three pathogenic genes (TCOF1, POLR1D and POLR1C) have been identified. In this study, we conducted mutational analysis on Chinese TCS patients to reveal a mutational spectrum of known causative genes and show phenotype-genotype data to provide more information for gene counselling and future studies on the pathogenesis of TCS. Twenty-two TCS patients were recruited from two tertiary referral centres, and Sanger sequencing for the coding exons and exon-intron boundaries of TCOF1, POLR1D and POLR1C was performed. For patients without small variants, further copy number variations (CNVs) analysis was conducted using high-density SNP array platforms. The Sanger sequencing overall mutation detection rate was as high as 86.3% (19/22) for our cohort. Fifteen TCOF1 pathogenic variants, including ten novel mutations, were identified in nineteen patients. No causative mutations in POLR1D and POLR1C genes and no CNVs mutations were detected. A suspected autosomal dominant inheritance case that implies germinal mosaicism was described. Our study confirmed that TCOF1 was the main disease-causing gene for the Chinese TCS population and revealed its mutation spectrum. We also addressed the need for more studies of mosaicism in TCS cases, which could explain the mechanism of autosomal dominant inheritance in TCS cases and benefit the prevention of TCS.

Phenotypic characterization and risk factors for microtia in East China, a case-control study.

OBJECTIVE: Although congenital microtia has been reported in various studies, little is known about the etiology of isolated and sporadic cases. The aim was to analyze potential risk factors for isolated and sporadic microtia using case-control study in East China. METHODS: The study analyzed data from the hospital-based recruitment for deliveries between 2007 and 2013. Nine hundred eleven patients with microtia enrolled in the phenotypic characterization analysis, and then were adjusted by sex, age, region, syndrome and family history to compare with 562 random normal controls for potential risk factors. RESULTS: Microtia is observed more often in males (69.7%), and the cases were typically unilateral (74.0%), right-sided (57.2%), sporadic (92.0%) and isolated (69.5%). Mothers of children with microtia were more likely to have suffered a periconceptional cold-like syndrome as well as to have had a history of previous spontaneous abortion. Inflammatory infection (aOR, 3.56; 95% CI, 2.07-6.13) and chemical exposure (aOR, 2.77; 95% CI, 1.78-4.32) was associated with a higher risk of microtia. However, threatened abortion was not the risk factor (aOR, 1.14; 95% CI, 0.78-1.67), using progesterone may increase the risk (aOR, 1.92; 95% CI, 1.03-3.59). CONCLUSION: The results of phenotypic characterization analysis were similar to other studies. By controlling the effects of potential confounders, some risk factors could be teratogens of isolated and sporadic microtia in East China.

[Analysis of correlation between congenital auricular deformities and middle ear malformations].

OBJECTIVE: To explore the potential value of knowing the relationship between congenital auricular deformities and middle ear malformations. METHODS: A total of 86 patients with congenital auricular deformities and middle ear malformations, including 51 males and 35 females, were admitted from January 2008 to December 2009 to the Eye Ear Nose and Throat Hospital of Fudan University. Fifty-eight patients had unilateral deformities (R:L = 34:24), while 28 were bilateral. One hundred and fourteen ears with congenital auricular deformities were included. High-resolution CT (HRCT) data was obtained from each patient. The auricular deformities were classified into three grades using the Marx H classification system. The modified Jahrsdoerfer grading system was used to score the malformations using HRCT data. The correlation between the grades of auricular deformities and scores of middle ear malformations was analyzed using Spearman rank correlation analysis. RESULTS: The Marx H grades of congenital auricular deformities were 12 patients with grade I, 25 patients with grade II and 77 patients with grade III, while their corresponding Jahrsdoerfer scores were 7.8 ± 2.4, 6.8 ± 2.6 and 6.0 ± 2.8, respectively. The statistical analysis suggested a trend of negative correlation between the Marx H grades of auricular deformities and the Jahrsdoerfer scores of middle ear malformations (r = -0.2386, P = 0.0106). CONCLUSION: There was a trend to a negative correlation between congenital auricular deformities and middle ear malformations.