Objective To study the SLC26A4 mutations in children with non -syndromic hearing loss by ge-netic testing method ,for the purpose of investigating etiology and mutation regularity of hearing loss ,and to provide basic information for the molecular diagnosis of hearing loss .Methods Blood samples and clinical data of 137 spo-radic cases with non -syndromic hearing loss and 126 normal controls were collected .The SLC26A4 gene of the pa-tients and normal controls were amplified by polymerase chain reaction (PCR) ,then subjected to automatic DNA se-quencing .Results Pathologic SLC26A4 mutations were identified in 23 out of 137 patients ,and in 23 out of 119 bi-lateral deafness ,mutate rate were 16 .79% and 19 .33% ,respectively .SLC26A4 mutations were identified in 19 out of 20(95% ) patients with bilateral LVA .A total of 11 mutations were identified in the present study ,including 4 novel mutations (E29K(c .85G>A) ,R79X(c .235C> T) ,C282G(c .844T>G) ,V285I(c .853G>A) )and 7 repor-ted mutations .In the present study ,IVS7-2A>G was the most common mutation ,and was detected in 19 out of 23(82 .61% ) patients with SLC26A4 mutations .Conclusion SLC26A4 mutations ,the common reason for non -syndromic hearing loss ,were closely related with LVA .IVS7-2A>G was the most common mutation in SLC26A4 mutant .

Objective To establish the laboratory and geography-specific reference intervals for thyroid hormones during pregnancy and changes of serum thyroid hormone in Wuhan. Methods According to NACB guidelines,a total of 1 186 female including in or without pregnancy were recruited in our hospital randomly when they came to routine antenatal clinic. The 2.5 th and 97.5 th percentiles were calculated as the reference intervals for specialty of serum thyroid function including serum thyroid stimulating hormone(TSH),serum free three io-dine thyroid(FT3),serum free thyroxine(FT4)levels during each trimester by chemiluminescence.Results On comparing to non-pregnant women,the serum thyroid hormone in pregnant women had significant difference as the following:(1)FT3 concentrations showed decreased median centile throughout gestation step by step;(2)FT4 lev-els in second and third trimester had slightly decreased;(3)TSH levels had significant decreased in first and sec-ond trimeste and had no significant difference between the early pregnancy and middle pregnancy,and had recoved to the similar level of before pregnancy in middle pregnancy and late pregnancy.Compared with control group,the serum thyroid function levels of pregnant women had significant differences in trimesters. There were 5.84%, 19.09% and 28.91% of women in the first,second and third trimester,respectively,with serum TSH higher than the upper reference limit,or lower than the lower reference limit.Conclusions Serum thyroid function had signifi-cant correlations with pregnancy in Wuhan area. To establish pregnancy-specific thyroid function reference inter-vals of local area can reduce underdiagnosis effectively in thyroid gland related diseases.

Objective To assess the clinical value of high throughput seuencing (HTS) in noninvasive prenatal testing (NIPT). Methods The results of NIPT of 2 256 cases of women with singleton pregnancy were retrospectively reviewed. Free fetal DNA in maternal peripheral blood was sequenced using HTS, and bioinformatic analysis techniques. Prenatal diagnosis was performed through amniocentesis when NIPT indicated high risks. High risk results from non-invasive screening of fetal chromosomal and prenatal diagnosis were compared. Results All of the 2, 256 specimens were successfully analyzed and 35 cases were found with fetal chromosomal high risks, with an overall detection rate of 0.58％, including 13 cases with high risk for trisomy 21, 1 with trisomy 18, 1 with trisomy 13, 15 with sex chromosome abnormality and 5 with other chromosomal structures abnormality. All the 34 cases had further prenatal diagnosis except 1 case of pregnant woman with high-risk 13-trisomy who took abortion directly and refused further examination. Among 12 cases with high risk for 21-trisomy, 1 with 18-trisomy, 5 with sex chromosome abnormalities and 1 with the deletion of chromosome, 3 were confirmed by traditional karyotyping and/or single nucleotide polymorphism microarray (SNP-array) technology. The coincidence rate of abnormally high risk results of NIPT detection in fetal chromosomal and prenatal diagnosis were 92.85％, 100％, 33.33％ and 20％respectively. Conclusion There is a relatively high positive coincidence rate when compared HTS for screening of high risk for trisomy 21, 18, 13 aneuploidy and prenatal diagnosis and HTS is reliable. While when it comes to the screening of sex chromosome and other chromosomal structures abnormality, HTS still need to be improved and optimized.

OBJECTIVE: To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. METHODS: Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. RESULTS: The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05). CONCLUSION CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Pregnancy, High-Risk ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Chromosome Disorders/genetics*

OBJECTIVE: To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development. METHODS: From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis. RESULTS: Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome. CONCLUSION Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.
Humans ; Ring Chromosomes ; Intellectual Disability/genetics* ; Turner Syndrome/genetics* ; Phenotype ; Heart Defects, Congenital/genetics*

Objective To explore the relationship between chromosomal abnormalities and diseases in children by analyzing chromosome karyotypes. Methods The chromosome karyotype analysis of peripheral lymphocytes in 5 329 children was performed. Results In all, abnormal karyotype were found in 1 723 cases (32.33％) , in which the numerical chromosome abnormalities were detected in 1 539 (89.32％) , following by 125 cases of structural chromosome abnormalities (7.25％) , 53 cases of sex reverse syndrome (3.08％) , and 6 cases of true hermaphroditism (0.35％). The chromosome polymorphism were detected in 228 cases (4.28％). Conclusions The numerical chromosome abnormalities is most frequent chromosomal aberration and is one of the important causes that result in mental retardation, growth delay and disorders of sex development in children.

Objective This study aims to establish a reference range of thyroid function indicators for women in different periods of pregnancy in Hubei Province.Methods Using the prospective method,1 487 healthy pregnant women who did pregnancy check-up at Wuhan Maternal and Child Healthcare Hospital from March 2017 to May 2018 were asked to complete questionnaires and whose serum samples were examined,aged (29 ± 4) years within the range of 20-41,include 498 in early pregnancy,525 in middle pregnancy,and 464 in late pregnancy.Then their thyroid stimulating hormone (TSH),free triiodothyronine (FT3) and free thyroxine (FT4) levels were determined using chemiluminescence immunoassay method to establish reference ranges of the indexes of thyroid function,reference ranges were in median (M) and percentage (P2.5-P97.5).At the same time,the newly established reference range was compared with the reference range recommended by the American Thyroid Association (ATA) guidelines to evaluate the thyroid function of 10 232 pregnant women in counties (cities,districts) of Hubei Province.Results Reference ranges in early pregnancy,middle pregnancy and late pregnancy were shown as follows,TSH:1.41 (0.19-4.26),1.45 (0.25-4.39),2.04 (0.51-5.10) mU/L;FT3:4.76 (3.78-16.01),4.65 (3.72-5.91),4.22 (3.41-5.33) pmol/L;FT4:63.71(47.40-86.25),58.28 (41.18-82.36),48.95 (33.41-66.82) nmol/L.The thyroid function assessment of pregnant women with the newly established reference range shows that the detection rate of thyroid dysfunction in pregnant women is was 13.58％ (1 390/10 232),which was lower than 37.98％ (3 886/10 232,x2 =102.58,P ＜ 0.05) diagnosed by the ATA guidelines.Conclusions The reference range of women's specific thyroid function indicators in different stages of pregnancy in Hubei Province is established.Compared with the reference range recommended by ATA,it is more suitable for thyroid function monitoring and thyroid disease screening for pregnant women in Hubei Province.