A Case Report of Neonatal Lupus Erythematosus with Liver Function Damage and Cytomegalovirus Colonization.

BACKGROUND: Neonatal lupus erythematosus (NLE) is an acquired autoimmune disease. NLE with liver function damage and cytomegalovirus colonization is rarely reported. METHODS: This case describes a newborn male's laboratory testing found sustained liver function damage when he came to see the doctor due to oral candidiasis. The cause was identified through clinical symptoms, laboratory tests, auxiliary examinations, and family history of the patient. RESULTS: The final diagnosis of the child was NLE with liver function damage and cytomegalovirus colonization according to comprehensive analysis and follow-up observation. CONCLUSIONS: NLE and cytomegalovirus colonization can both lead to liver function damage. When the organ function of newborns is abnormal, it is necessary to promptly investigate the cause and determine whether it is NLE.

Genetic Basis of Congenital Central Hypothyroidism in Children: Expanding the Mutational Spectrum of POU1F1 and ATP6V0A4.

Objective: Congenital central hypothyroidism (CCH) is a rare disorder poorly described in childhood and adolescence. The current knowledge on the genetic bases of CCH is scarce. The purpose of this study was to analyze the clinical characteristics and molecular genetic basis of CCH in children. Methods: We conducted a thorough evaluation of the clinical features in children diagnosed with CCH. Genomic DNA was extracted from peripheral blood of both children and their parents, and chromosomal microarray analysis and whole-exome sequencing were performed. Candidates for single nucleotide variants were validated using Sanger sequencing and were classified according to the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines. Results: Two cases with likely pathogenic variants were detected by whole-exome sequencing. Individual 1 carried a novel homozygous ATP6V0A4 c.1418C>T (p.Ser473Phe) variant and a novel heterozygous POU1F1 c.416G>A. (p.Arg139Gln) variant. Individual 2 had a novel homozygous POU1F1 c.212C>T (p.Ala71Val) variant. The chromosomal microarray detected the presence of a 24 Mb heterozygous deletion (LOH: loss of heterozygosity) in the p12.1p13.13 region of chromosome 2 in individual 3, and the copy number variant was unknown of clinical significance. Conclusion: Our study employed chromosomal microarray and whole-exome sequencing to investigate central hypothyroidism in seven children, leading to the detection of genetic anomalies in three individuals. The identification of novel variants has contributed to the expanded genetic spectrum of POU1F1 and ATP6V0A4 associated with pediatric central hypothyroidism.

Estimation of homocysteine concentration as an indicator of foetal death in pregnant Chinese women with preeclampsia: A case-control study.

INTRODUCTION: This study evaluated whether changes in homocysteine concentrations in pregnant women with preeclampsia (PE) might be useful for predicting foetal death. MATERIALS AND METHODS: This study evaluated 1,368 PE women at two Chinese centres. Medical records were reviewed to collect data regarding maternal age, homocysteine concentrations and other clinical parameters. RESULTS: Maternal serum homocysteine concentrations were significantly higher in the group with PE than control. Significant differences (p < 0.05) were also observed between the foetal death and survival groups in terms of body mass index, neonatal weight, previous deliveries, gestation length and adverse pregnancy history. Multivariate logistic regression analysis revealed that upper-quartile homocysteine concentration was a significant risk factor of foetal death in the group with PE, and overall survival rate of patients with high homocysteine concentrations during pregnancy was significantly lower than those with low level (p < 0.05). CONCLUSIONS: Our results indicate that foetal death was associated with upper-quartile homocysteine concentrations in the group with PE, it can be an indicator of foetal death throughout the pregnancy.

Performance evaluation of optical platelet counting of BC-6000Plus automated hematology analyzer.

BACKGROUND: The BC-6000Plus (Mindray, Shenzhen, China) is a recently developed hematology analyzer that utilizes fluorescent technology. Based on fluorescent nucleic acid stain and optical detection, the optical platelet counting (PLT-O) on the BC-6000Plus has strong anti-interference potential in platelet (PLT) detection. Its Auto 8×PLT-O Counting Tech can be automatically triggered in low-PLT samples, which enables the PLT-O on the BC-6000Plus to count low PLT more efficiently. Here, we evaluated the performance of the BC-6000Plus automated hematology analyzer in optical PLT counting. METHODS: The basic features (including blank counting, carryover, trueness, and accuracy) of the BC-6000Plus for PLT counting were evaluated according to the Analytical Quality Specifications for Routine Tests in Clinical Hematology (WST 406-2012). Low-PLT samples with a PLT count of below 100×109/L were selected for repeatability tests. Meanwhile, the potential correlations of BC-6000Plus with the XN-L 350 and manual microscopy within different PLT ranges or under interferences of small red blood cells (RBCs) or PLT aggregation were analyzed. RESULTS: The PLT-O on BC-6000Plus met the technical requirements of PLT counting in terms of blank count, carryover, trueness, and accuracy. The repeatability of the enhanced mode (PLT-O 8×) on the BC-6000Plus was better than that of the XN-L 350 in three low PLT count ranges, including 10-20, 20-60, and 60-100 (×109/L). Under the interference-free conditions, the BC-6000Plus correlated well with the XN-L 350 in different PLT counting ranges. Under the interferences of small RBCs and PLT aggregation, the PLT-O on BC-6000Plus correlated better with microscopy than with the platelet impedance count (PLT-I). CONCLUSIONS: The PLT-O on BC-6000Plus can meet the technical requirements of PLT counting in terms of blank counting, carryover rate, trueness, and accuracy. The PLT-O 8× has good repeatability, correlates well with the XN-L 350, and demonstrates good anti-interference ability. It can thus meet the needs of blood cell analysis in clinical settings.

A Review on Map-Merging Methods for Typical Map Types in Multiple-Ground-Robot SLAM Solutions.

When multiple robots are involved in the process of simultaneous localization and mapping (SLAM), a global map should be constructed by merging the local maps built by individual robots, so as to provide a better representation of the environment. Hence, the map-merging methods play a crucial rule in multi-robot systems and determine the performance of multi-robot SLAM. This paper looks into the key problem of map merging for multiple-ground-robot SLAM and reviews the typical map-merging methods for several important types of maps in SLAM applications: occupancy grid maps, feature-based maps, and topological maps. These map-merging approaches are classified based on their working mechanism or the type of features they deal with. The concepts and characteristics of these map-merging methods are elaborated in this review. The contents summarized in this paper provide insights and guidance for future multiple-ground-robot SLAM solutions.

Rate of the HIV Transmission and Associated Factors Among HIV-Exposed Infants in Guangxi, China: 2014-2019.

This study aims to evaluate the epidemiological characteristics of mother-to-child transmission (MTCT) of HIV and identify the possible factors leading to infant HIV infection using a retrospective cohort study of early infant diagnosis (EID). Information on a total of 3,145 exposed infant-mother pairs was collected from the EID platform from July 2014 to December 2019. The MTCT rate was 2.1%. Spatial-temporal maps showed that rates varied by year and by region, with four districts (Baise, Guigang, Guilin, and Hechi) maintaining rates of >2.0% in 2019. The rate of antiretroviral therapy (ART) use was 94.4%, with a gradual increase in prescriptions of highly active ART (HAART) from 83.0% in 2014 to 92.4% in 2019. A majority of 99.5% of infants were receiving artificial feeding. Factors associated with MTCT were ART use (odds ratio [OR] = 0.065, confidence interval [95% CI] = 0.035-0.121) and artificial feeding (OR = 0.091, 95% CI = 0.018-0.452). HAART was more helpful in decreasing the risk of MTCT compared with monotherapy (OR = 0.115, 95% CI = 0.014-0.933). ART during the postpartum period correlated with an increased risk (OR = 11.579, 95% CI = 1.402-95.960) compared with use of ART during pregnancy. This study indicates that MTCT rate of HIV is decreasing meaningfully in Guangxi. Some areas still face challenges in elimination of MTCT and need further resources and interventions. Future program planning should take into consideration the fact that ART use-in particular the use of HAART or ART during pregnancy-and replacement feeding may contribute to the prevention of MTCT.

Etiology and Outcome of non-immune Hydrops Fetalis in Southern China: report of 1004 cases.

Non-immune hydrops fetalis (NIHF) is a complex condition with a high mortality and morbidity rate. Here we report the etiology and outcome of 1004 fetuses with NIHF, in a large single Maternal and Children's hospital of Southern China, since the year of 2009 to 2016. Among these 1004 fetuses with NIHF, the etiology was identified prenatally in 722 of them (72%). The most common ones were hematologic diseases and chromosomal abnormalities. There were eight spontaneous abortions, 18 intrauterine fetal demise, 672 pregnancy terminations and 87 were lost to follow-up. 219 of the 1004 fetuses were live-born and the overall survival rate was 21.8% at this point. After birth 16 perinatal or early neonatal deaths were encountered and five lost to follow-up. Of the remaining 198 newborns, 153 thrived without apparent morbidity. The most significant factors associated with mortality were prematurity and low birthweight. In conclusion, we described the largest report of underlying causes and outcome of NIHF in Southern China. Etiologies were identified for 72% of 1004 fetuses with NIHF. And two poor prognostic factors for survival are preterm birth at less than 36.5 weeks and birthweight lower than 2575 g respectively.

[Genetic testing and pregnancy outcome of 337 fetuses with urinary system anomalies].

OBJECTIVE: To explore the genetic basis and pregnancy outcome of fetuses with urinary system anomalies. METHODS: Ultrasonographic features, genetic testing and pregnancy outcomes of 337 fetuses with urinary system anomalies identified by prenatal ultrasonograhy were collected for analysis. RESULTS: Ultrasonographic features of the fetuses were mainly characterized by hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia. Thirty four fetuses (10.1%) were found to harbor a genetic defect, including 14 numerical chromosomal disorders, 10 structural chromosomal aberrations, and 10 pathogenic copy number variations (CNVs). In 31 cases, the parents elected induced labor. For the 303 fetuses with negative findings, 142 were born by spontaneous delivery or Caesarean section, 48 cases underwent induced labor, 1 case had miscarriage, and the remaining 112 cases had unknown or missed pregnancy outcomes. CONCLUSION: Hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia are the most common findings among fetuses with urinary system anomalies. Approximately 10.1% of such fetuses are positive by genetic testing.

State Transition for Statistical SLAM Using Planar Features in 3D Point Clouds.

There is a large body of literature on solving the SLAM problem for various autonomous vehicle applications. A substantial part of the solutions is formulated based on using statistical (mainly Bayesian) filters such as Kalman filter and its extended version. In such solutions, the measurements are commonly some point features or detections collected by the sensor(s) on board the autonomous vehicle. With the increasing utilization of scanners with common autonomous cars, and availability of 3D point clouds in real-time and at fast rates, it is now possible to use more sophisticated features extracted from the point clouds for filtering. This paper presents the idea of using planar features with multi-object Bayesian filters for SLAM. With Bayesian filters, the first step is prediction, where the object states are propagated to the next time based on a stochastic transition model. We first present how such a transition model can be developed, and then propose a solution for state prediction. In the simulation studies, using a dataset of measurements acquired from real vehicle sensors, we apply the proposed model to predict the next planar features and vehicle states. The results show reasonable accuracy and efficiency for statistical filtering-based SLAM applications.

Chromosomal microarray and whole exome sequencing identify genetic causes of congenital hypothyroidism with extra-thyroidal congenital malformations.

BACKGROUND: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder. Although most patients present with isolated CH, some patients present with CH and extra-thyroidal congenital malformations (ECMs), for which less is known about the underlying genetics. The aim of this study was to investigate the genetic mechanisms in patients with CH and ECMs using chromosomal microarray (CMA) and whole exome sequencing (WES). METHODS: Peripheral venous blood samples were collected from 16 patients with CH and ECMs. Genomic DNA was extracted from peripheral blood leukocytes. CMA and WES were performed to detect copy number and single nucleotide variants. RESULTS: CMA identified clinically significant copy number variants in 7 patients consistent with their phenotypes. For 6 of them, the genotype and phenotype suggested a syndromic diagnosis, and the remaining patient carried a pathogenic microdeletion and microduplication including GLIS3. WES analysis identified 9 different variants in 7 additional patients. The variants included 2 known mutations (c.1096C>T (p.Arg366Trp) in KCNQ1 and c.848C>A (p.Pro283Gln) in NKX2-5) and 7 novel variants: one nonsense mutation (c.4330C>T (p.Arg1444*) in ASXL3), one frameshift mutation (c.1253_1259delACTCTGG (p.Asp418fs) in TG), three missense variants (c.1472C>T (p.Thr491Ile) in TG, c.4604A>G (p.Asp1535Gly) in TG, and c.2139G>T (p.Glu713Asp) in DUOX2, and two splice site variants (c.944-1G>C and c.3693 + 1G>T) in DUOX2. CONCLUSIONS: We report the first genetic study of CH patients with ECMs using CMA and WES. Overall, our detection rate for pathogenic and possibly pathogenic variants was 87.5% (14/16). We report 7 novel variants, expanding the mutational spectrum of TG, DUOX2, and ASXL3.

Genetic Testing and Pregnancy Outcome Analysis of 362 Fetuses with Congenital Heart Disease Identified by Prenatal Ultrasound / Análise de Teste Genético e de Desfecho da Gestação de 362 Fetos com Cardiopatia Congênita Identificados por Ultrassom Pré-Natal

Abstract Background: Congenital heart defects (CHD), as the most common congenital anomaly, have been reported to be associated with chromosomal abnormalities. Currently, patients with CHD are routinely offered karyotyping and chromosomal microarray (CMA) testing, but the genotype-phenotype relationship has not yet been fully established. Objective: To determine the type and frequency of chromosomal abnormalities in fetuses with CHD and to analyze pregnancy outcomes of fetuses with heart abnormalities caused by different genetic factors. Methods: A total of 362 cases of CHD were enrolled from 2009 to 2016. Detailed ultrasound and laboratory examinations, including karyotyping and CMA, were performed. Outcome was obtained from discharge summaries. Results: Of the 362 fetuses, 220 were found with an isolated CHD, and 142 had CHD with extracardiac anomaly. Among these 362 fetuses, 140 were identified with a genetic cause, including 111 cases with aneuploidy, 10 cases with abnormality of chromosomal structure by karyotyping and 19 cases with pathogenic or likely pathogenic copy-number variations (CNVs) by CMA. The detection rate is close to 38.7%. Only one (identified as trisomy 18 syndrome) in 140 positive cases resulted in perinatal death, with the others being induced. The remaining 222 cases had negative results for both genetic testing and of these cases, 56 resulted in induced labor, and 77 had natural childbirth or caesarean births. The pregnancy outcome of the remaining 89 cases was uncertain. Conclusions: Karyotyping and CMA are effective and accurate prenatal genetic techniques for identifying fetal chromosomal abnormalities associated with cardiac defects, and this can assist clinical doctors to perform appropriate genetic counselling with regard to the etiology and outcome of CHD.

Resumo Fundamento: As cardiopatias congênitas (CCs) são as anomalias congênitas mais comuns, e têm sido associadas a anormalidades cromossômicas. Atualmente, a cariotipagem e a análise cromossômica por microarray (CMA) são oferecidas rotineiramente aos pacientes, mas a relação genótipo-fenótipo ainda não foi totalmente estabelecida. Objetivo: Determinar o tipo e a frequência das anomalias cromossômicas em fetos com CC e analisar os desfechos da gestação de fetos com anormalidades cardíacas causadas por diferentes fatores genéticos. Métodos: No total, foram admitidos 362 casos de CC entre 2009 e 2016. Ultrassonografia e exames laboratoriais detalhados foram realizados, incluindo cariotipagem e CMA. O resultado foi obtido a partir das folhas de epicrise. Resultados: Dos 362 fetos, 220 apresentaram doença coronariana isolada e 142 apresentaram doença coronariana com anomalia extracardíaca. Entre esses 362 fetos, foram identificados 140 com causa genética, incluindo 111 casos com aneuploidia, 10 casos com anormalidade da estrutura cromossômica por cariotipagem e 19 casos com variações no número de cópias (CNVs) patogênicas ou provavelmente patogênicas por CMA. A taxa de detecção é de aproximadamente 38,7%. Apenas um (identificado como síndrome da trissomia do cromossomo 18) em 140 casos positivos resultou em morte perinatal, com as demais sendo induzidas. Os 222 casos restantes tiveram resultados negativos para ambos os testes genéticos e, destes, 56 resultaram em trabalho de parto induzido e 77 tiveram partos naturais ou cesarianas. O desfecho da gravidez dos 89 casos restantes foi incerto. Conclusões: A cariotipagem e a CMA são técnicas genéticas pré-natais eficazes e precisas para a identificação de anomalias cromossômicas fetais associadas a defeitos cardíacos, e isso pode ajudar os médicos a realizar aconselhamento genético adequado com relação à etiologia e ao desfecho das cardiopatias congênitas.

Genetic Testing and Pregnancy Outcome Analysis of 362 Fetuses with Congenital Heart Disease Identified by Prenatal Ultrasound.

BACKGROUND: Congenital heart defects (CHD), as the most common congenital anomaly, have been reported to be associated with chromosomal abnormalities. Currently, patients with CHD are routinely offered karyotyping and chromosomal microarray (CMA) testing, but the genotype-phenotype relationship has not yet been fully established. OBJECTIVE: To determine the type and frequency of chromosomal abnormalities in fetuses with CHD and to analyze pregnancy outcomes of fetuses with heart abnormalities caused by different genetic factors. METHODS: A total of 362 cases of CHD were enrolled from 2009 to 2016. Detailed ultrasound and laboratory examinations, including karyotyping and CMA, were performed. Outcome was obtained from discharge summaries. RESULTS: Of the 362 fetuses, 220 were found with an isolated CHD, and 142 had CHD with extracardiac anomaly. Among these 362 fetuses, 140 were identified with a genetic cause, including 111 cases with aneuploidy, 10 cases with abnormality of chromosomal structure by karyotyping and 19 cases with pathogenic or likely pathogenic copy-number variations (CNVs) by CMA. The detection rate is close to 38.7%. Only one (identified as trisomy 18 syndrome) in 140 positive cases resulted in perinatal death, with the others being induced. The remaining 222 cases had negative results for both genetic testing and of these cases, 56 resulted in induced labor, and 77 had natural childbirth or caesarean births. The pregnancy outcome of the remaining 89 cases was uncertain. CONCLUSIONS: Karyotyping and CMA are effective and accurate prenatal genetic techniques for identifying fetal chromosomal abnormalities associated with cardiac defects, and this can assist clinical doctors to perform appropriate genetic counselling with regard to the etiology and outcome of CHD.

Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates.

The aim of this study is to assess the disease incidence and mutation spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangxi, China, and to determine an optimal cutoff value to identify heterozygous female neonates. A total of 130, 635 neonates were screened from the year of 2013 to 2017. Neonates suspected for G6PD deficiency were further analyzed by quantitatively enzymatic assay and G6PD mutation analysis. The overall incidence of G6PD deficiency was 7.28%. A total of 14 G6PD mutations were identified, and different mutations lead to varying levels of G6PD enzymatic activities. The best cut-off value of G6PD activity in male subjects is 2.2 U/g Hb, same as conventional setting. In female population, however, the cut-off value is found to be 2.8 U/g Hb (sensitivity: 97.5%, specificity: 87.7%, AUC: 0.964) to best discriminate between normal and heterozygotes, and 1.6 U/g Hb (sensitivity: 82.2%, specificity: 85.9%, AUC: 0.871) between heterozygotes and deficient subjects. In conclusion, we have conducted a comprehensive newborn screening of G6PD deficiency in a large cohort of population from Guangxi, China, and first established a reliable cut-off value of G6PD activity to distinguish heterozygous females from either normal or deficient subjects.

Mutation screening of the GLIS3 gene in a cohort of 592 Chinese patients with congenital hypothyroidism.

OBJECTIVES: Defects in the human GLI-similar 3 (GLIS3) gene are reported to be a rare cause of congenital hypothyroidism (CH) and neonatal diabetes. The aim of this study was to examine the prevalence of GLIS3 mutation among CH patients in the Guangxi Zhuang Autonomous Region of China and to define the relationships between GLIS3 genotypes and clinical phenotypes. METHODS: Blood samples were collected from 592 patients with CH in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the GLIS3 gene with their exon-intron boundaries were screened by next-generation sequencing (NGS) and CNVplex®. Chromosomal microarray analysis (CMA) was performed to detect the existence of the adjacent gene deletion. RESULTS: NGS and CNVplex® analysis of GLIS3 in 592 CH patients revealed two different variations in two individuals (2/592, 0.3%). Patient 1 was the paternal allele of 9p24.3p23 heterozygous deletion including the whole GLIS3 gene, and patient 2 was heterozygous for c.2159G>A (p.R720Q) GLIS3 variant combined with compound heterozygous DUOX2 mutations (p.R683L/p.L1343F). CONCLUSIONS: Our study indicated that the prevalence of GLIS3 variations was 0.3% among studied Chinese CH patients. Multiple variations in one or more CH associated genes can be found in one patient. We found a novel GLIS3 variation c.2159G>A (p.R720Q), thereby expanding the variation spectrum of the gene.

The incidence of congenital hypothyroidism (CH) in Guangxi, China and the predictors of permanent and transient CH.

BACKGROUND: The incidence of congenital hypothyroidism (CH) differs significantly among different ethnicities and regions, and early differentiation of transient CH is important to avoid unnecessary prolonged treatment with L-T4. OBJECTIVE: To investigate the incidence of CH based on the newborn screening program in Guangxi Zhuang Autonomous Region, China, and to analyze the predictors that might allow for an early differentiation between permanent (P) and transient (T) CH. DESIGN AND METHODS: Data from newborn screening program over a seven-year period (January 2009 to January 2016) at Guangxi Maternal and Child Health Hospital are analyzed. Blood samples were collected on filter paper between 3 and 7 days after birth, and TSH level was measured by time-resolved fluorescence assay. Individuals with increased TSH (TSH ≥ 8 IU/L) levels detected by newborn screening were recalled for further evaluation. Serum TSH, FT3 and FT4 were determined by electrochemiluminescence assay using venous blood samples. Diagnosis of CH is based on elevated TSH levels (>10 IU/L) and decreased FT4 levels (<12 pmol/L). Patients with elevated TSH levels and normal FT4 levels were diagnosed as hyperthyrotropinemia. Permanent or transient CH was determined by using the results of thyroid function tests after temporary withdrawal of L-T4 therapy at approximately 2-3 years of age. RESULTS: Among 1,238,340 infants in the newborn screening program, 14,443 individuals were recalled for reevaluation (re-call rate 1.18%), 911 and 731 individuals were subsequently determined to have hyperthyrotropinemia and CH respectively; thus, a prevalence of 1:1359 and 1:1694 for hyperthyrotropinemia and CH. Of the 731 patients with CH, 161 patients were diagnosed with permanent CH (PCH), and 159 patients were diagnosed with transient CH (TCH), the other 411 patients are too young to determine their subtypes. Patients with PCH required an increasing dose of L-T4 during the first few years, whereas patients with TCH required a decreased dose of L-T4. The TSH levels at diagnosis and the dose of L-T4 used were significantly higher in PCH cases than in transient cases. The FT4 levels at diagnosis were significantly lower in PCH cases than in TCH cases. The TSH levels at diagnosis, FT4 levels at diagnosis and L-T4 doses at 90 days were evaluated as predictors for differentiating PCH and TCH, and their accuracy at their respective optimal cutoffs were determined to be 60.6%, 66.7% and 93.9%, respectively. CONCLUSIONS: The CH incidence in Guangxi Zhuang Autonomous Region is slightly higher (1:1694) compared to the worldwide levels (1/2000-1/4000). The PCH and TCH ratio is close to 1; thus, the estimated PCH incidence is 1/3388, which is similar to reported worldwide average incidence (1/3000). The L-T4 dose required at 90 days (>30 µg/day) has the highest predictive value for PCH. Earlier differentiation of PCH and TCH helps to determine appropriate treatment course.

Mosaic UPD(7q)mat in a patient with silver Russell syndrome.

BACKGROUND: Silver-Russell syndrome (SRS) is one of the imprinting disorders characterized by prenatal and postnatal growth restriction, relative macrocephaly, body asymmetry and characteristic facial features. ~ 10% of SRS cases are known to be associated with maternal uniparental disomy of chromosome 7 (UPD(7)mat). Mosaic maternal segmental UPD of 7q (UPD(7q)mat) is very rare, had only been described in one case before. CASE PRESENTATION: We reported a second case of mosaic segmental UPD involving 7q. The patient presented with dysmorphic features including thin and short stature, triangular face, moderate protruding forehead, relative macrocephaly, fifth toe clinodactyly and irregular teeth, meeting the clinical diagnosed criteria of SRS. This case indicated that ~ 80% of mosaic UPD(7q)mat lead to the manifestation of main phenotypes of Silver-Russell syndrome. CONCLUSIONS: Our case support the notion that there are genes control postnatal growth on long arm of chromosome 7 and indicate that ~ 80% of UPD(7q)mat mosaicism level was contributed to the SRS phenotype.

[Application of SNP-array technology in the genetic analysis of pediatric patients with growth retardation].

OBJECTIVE: To explore the value of single nucleotide polymorphism array (SNP-array) for the analysis of pediatric patients with growth retardation. METHODS: One hundred eighty one children with growth retardation were enrolled. DNA was extracted from peripheral samples from the patients, and whole genome copy number variations (CNVs) were detected using Illumina Human Cyto SNP-12. All identified CNVs were further analyzed with reference to databases including ClinGen, ClinVar, DECIPHER, OMIM and DGV as well as comprehensive review of literature from PubMed to determine their pathogenicity. RESULTS: Forty seven patients (26%) with abnormal CNVs were detected, which included 12 known microdeletions/microduplications syndrome (26%), 10 pathogenic non-syndromic CNVs (21%), 3 numerical chromosome aberrations (6%), 3 unbalanced translocations (6%), 4 pathogenic mosaicisms (9%) and 15 cases with unknown clinical significance (32%). After excluding obvious numerical and/or structural chromosomal abnormalities, this study has detected 15 pathogenic microdeletions/microduplications sized 5 Mb or less, which may be missed by routine chromosomal karyotyping. In addition, there were 3 cases with loss of heterozygoisty (LOH) containing known or predicted imprinting genes as well as 2 cases with suspected parental consanguinity. CONCLUSION: SNP-array technology is a powerful tool for the genetic diagnosis of children with growth disorders with advantages of high resolution and improved accuracy.

Next-generation sequencing analysis of twelve known causative genes in congenital hypothyroidism.

BACKGROUND: Gene variants have been reported to be associated with congenital hypothyroidism (CH), the purpose of this study was to analyze the mutation spectrum and prevalence of 12 known causative genes (TSHR, PAX8, NKX2.1, NKX2.5, FOXE1, DUOX2, TG, TPO, GLIS3, NIS, SLC26A4 and DEHAL1) in CH in China. METHODS: Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. All exons and their exon-intron boundary sequences of the 12 known CH associated genes in 66 CH patients were screened by next-generation sequencing (NGS). RESULTS: NGS analysis of 12 known CH associated genes revealed that 32 patients (32/66, 48.5%) were detected to have at least one potentially functional variant. 21, 9, 1, 1, 1 and 1 patients were found to have potential pathogenic variants in DUOX2, TG, PAX8, SLC26A4, TSHR and TPO genes, respectively. Novel variants included one DUOX2 and one TPO missense variants of unknown significance (VUS). CONCLUSION: Our study expands the mutation spectrum of DUOX2 and TPO genes. 48.5% CH patients had at least one potential pathogenic variant. We found relatively high frequency of DUOX2 (31.8%) and TG (13.6%) mutations in our cohort.

Next-generation sequencing analysis of TSHR in 384 Chinese subclinical congenital hypothyroidism (CH) and CH patients.

BACKGROUND: Defects in the human TSHR gene are reported to be one of the causes of CH due to thyroid dysgenesis, the purpose of this study was to examine the TSHR mutation spectrum and prevalence in congenital hypothyroidism (CH) and subclinical congenital hypothyroidism (SCH) patients in the Guangxi Zhuang Autonomous Region of China and to evaluate the genotype-phenotype correlations. METHODS: Blood samples were collected from 384 patients including 240 CH and 144 SCH patients in Guangxi, China. Genomic DNA was extracted from peripheral blood leukocytes. All exons of the 11 known CH associated genes including TSHR together with their exon-intron boundaries were screened by next-generation sequencing (NGS). RESULTS: NGS analysis of TSHR revealed nine different variants in ten individuals. Six (4.2%) of 144 patients with SCH were found to harbor monoallelic TSHR variants. Four (1.6%) of 240 patients with CH harbored TSHR variants combined with another monoallelic mutation in either DUOX2 or TG gene. The present study identified five novel variants c.1838A>G (p.Y613C), c.1576G>A (p.A526T), c.2087T>G (p.F696C), c.1631G>A (p.G544E) and c.2051C>A (p.A684D) in TSHR, seven known pathogenic variants c.1349G>A (p.R450H), c.326G>A (p.R109Q), c.2066T>G (p.V689G) and c.2272G>A (p.E758K) in TSHR, IVS3+2T>G in TG, and c.1588A>T (p.K530X) and c.2635G>A (p.E879K) in DUOX2. The previously reported hotspot mutation p.R450H was found in only one SCH patient. CONCLUSION: The prevalence of TSHR mutations was 1.6% in CH patients and 4.2% in SCH patients in Guangxi Zhuang Autonomous Region of China. Monoallelic TSHR pathogenic variants were associated with SCH, while TSHR pathogenic variants combined with monoallelic mutations in DUOX2 or TG gene might contribute to CH. Our study expands the TSHR mutation spectrum and provides the best estimation of mutation rate for SCH and CH patients in this Chinese population.

A rare occurrence of two large de novo duplications on 1q42-q44 and 9q21.12-q21.33.

De novo partial distal 1q trisomy is uncommon and mostly occurs in combination with monosomy of another chromosome due to a parental translocation. Distal 1q trisomy co-occurring with another de novo duplication on a separate chromosome is extremely rare. Here, we reported a patient carrying two large de novo interstitial duplications including a 20Mb duplication at 1q42-q44 and a 14.2Mb duplication at 9q21.12-q21.33. The patient presented with features of pre- and postnatal growth retardation, low birth weight, failure to thrive, developmental delay and frequent infection. Her dysmorphic features included macrocephaly, prominent forehead, triangular face, wide fontanelle, hypertelorism, flat nasal bridge, tented mouth, micrognathia, protruding and low-set ears, slender limbs with toe-walking appearance. In addition, she presented with subdural hematoma. The clinical presentations of this patient are mostly consistent with those of distal 1q trisomy syndrome or 9q interstitial duplication. The interstitial 1q trisomy may have contributed to the macrocephaly, prominent forehead and limb abnormalities of our patient. Either or both de novo duplications could have contributed to the features of growth retardation, developmental delay and dysmorphic features including hypertelorism, low-set ears and abnormal nose/nasal bridge.