Comparison of the Reference Intervals Used for the Evaluation of Maternal Thyroid Function During Pregnancy Using Sequential and Nonsequential Methods

Background： Maternal thyroid dysfunction is common during pregnancy, and physiological changes during pregnancy can lead to the overdiagnosis of hyperthyroidism and misdiagnosis of hypothyroidism with nongestation-specific reference intervals. Our aim was to compare sequential with nonsequential methods for the evaluation of thyroid function in pregnant women. Methods： We tested pregnant women who underwent their trimester prenatal screening at our hospital from February 2011 to September 2012 for serum thyroid stimulating hormone （TSH） and free thyroxine （FT4） using the Abbott and Roche kits. There were 447 and 200 patients enrolled in the nonsequential and sequential groups, respectively. The central 95% range between the 2.5th and the 97.5th percentiles was used as the reference interval for the thyroid function parameter. Results： The nonsequential group exhibited a significantly larger degree of dispersion in the TSH reference interval during the 2nd and 3rd trimesters as measured using both the Abbott and Roche kits （all P 〈 0.05）. The TSH reference intervals were significantly larger in the nonsequential group than in the sequential group during the 3rd trimester as measured with both the Abbott （4.95 vs. 3.77 mU/L, P 〈 0.001） and Roche kits （6.62 vs. 5.01 mU/L, P〈 0.004）. The nonsequential group had a significantly larger FT4 reference interval as measured with the Abbott kit during all trimesters （ 12.64 vs. 5.82 pmol/L; 7,96 vs. 4.77 pmol/L; 8.10 vs. 4.77 pmol/L, respectively, all P 〈 0.05）, whereas a significantly larger FT4 reference interval was only observed during the 2nd trimester with the Roche kit （7.76 vs. 5.52 pmol/L, P = 0.002）. Conclusions： It was more reasonable to establish reference intervals for the evaluation of maternal thyroid function using the sequential method during each trimester of pregnancy. Moreover, the exclusion of pregnancy-related complications should be considered in the inclusion criteria for thyroid function tests.

Integrated facial analysis and targeted sequencing identifies a novel KDM6A pathogenic variant resulting in Kabuki syndrome

Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases.In this study,a Chinese woman,presenting with characteristic facial features of KS,came for pre-pregnancy consultation.We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling.Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants,respectively.The candidate variant was verified by Sanger sequencing.We identified a novel de novo KDM6A pathogenic variant(c.3521G>A)in the woman,which was in line with the Face2Gene analysis result.Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A.Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.