Clinical characteristics and genetic analysis of a child with Galactosemia due to compound heterozygous variants of GALT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of a child with Galactosemia.@*METHODS@#A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing.@*RESULTS@#Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR).@*CONCLUSION@#Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.

Analysis of clinical characteristics and ACADM gene variants in four children with Medium chain acyl-CoA dehydrogenase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).@*METHODS@#Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES).@*RESULTS@#All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant.@*CONCLUSION@#The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.

Phenotypic and genetic analysis of a child with partial trisomy 7q / 中华医学遗传学杂志

OBJECTIVE@#To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation.@*METHODS@#A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).@*RESULTS@#Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child.@*CONCLUSION@#The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.

Genetic analysis of a case with 11β hydroxylase deficiency caused by CYP11B2/CYP11B1 chimeric gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze a child with 11β hydroxylase deficiency (11β-OHD) due to CYP11B2/CYP11B1 chimeric gene.@*METHODS@#Clinical data of the child who was admitted to Henan Children's Hospital on August 24, 2020 were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RT-PCR and Long-PCR were carried out to verify the presence of chimeric gene.@*RESULTS@#The patient, a 5-year-old male, had featured premature development of secondary sex characteristics and accelerated growth, and was diagnosed with 21 hydroxylase deficiency (21-OHD). WES revealed that he has harbored a heterozygous c.1385T>C (p.L462P) variant of the CYP11B1 gene, in addition to a 37.02 kb deletion on 8q24.3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1385T>C (p.L462P) was rated as a likely pathogenic variant (PM2_Supporting+PP3_Moderate+PM3+PP4). The results of RT-PCR and Long-PCR suggested that CYP11B1 and CYP11B2 genes have recombined to form a CYP11B2 exon 1~7/CYP11B1 exon 7~9 chimeric gene. The patient was diagnosed as 11β-OHD and effectively treated with hydrocortisone and triptorelin. A healthy fetus was delivered following genetic counseling and prenatal diagnosis.@*CONCLUSION@#11β-OHD may be misdiagnosed as 21-OHD due to the potential CYP11B2/CYP11B1 chimeric gene, which will require multiple methods for the detection.

Whole-genome characterization and traceability analysis of the first COVID-19 outbreak caused by Omicron variant in Henan Province / 中华微生物学和免疫学杂志

Objective:To analyze the whole genome of Omicron variants causing the first local Omicron outbreak in Henan Province and to investigate the mutations in the SARS-CoV-2 genome for source tracing.Methods:Respiratory tract samples from COVID-19 cases in the Omicron outbreak in Henan Province from January 7 to 29, 2022 were subjected to whole-genome sequencing and sequence alignment analysis. Whole-genome identity, variations and evolution of the Omicron variants were analyzed.Results:Through high-throughput sequencing, the whole-genome sequences of SARS-CoV-2 were obtained from 120 cases, which accounted for 25.64% (120/468) of all COVID-19 cases in Anyang during the same period. Compared with the genome of Wuhan reference strain (NC_045512.2), there were 57-59 nucleotide mutation sites in the 120 whole genome sequences, and one or two nucleotide mutation sites were added to the shared 57 nucleotide sites. All of the 120 strains were VOC/Omicron (BA.1.1) variants and shared high homology. The whole-genome sequence obtained from the first case A contained 57 nucleotide mutation sites, while apart from the 57 identical nucleotide mutation sites, one specific mutation site (C1594T) was found in the whole-genome sequence obtained from the first case B, suggesting that the two cases were in the same transmission chain. After comparing with the database of domestic and imported cases by the Chinese Center for Disease Control and Prevention and the Henan Provincial Center for Disease Control and Prevention, it was found that the current outbreak was linked with the same transmission chain as the existing local epidemics in other provinces. Moreover, epidemiological investigation showed that on January 2, case A had come into contact with her cousin and his family who returned from an affected area outside the province.Conclusions:Based on the gene sequencing results and epidemiological investigation, the COVID-19 outbreak in Anyang city, Henan Province was a local epidemic and the source of it was a college student who returned to Anyang city from other province on December 28, 2021. These infections were linked to the same transmission chain as the existing local infection in other provinces.

Analysis of influencing factors and construction of predictive nomogram on 15-minute retention rate of indocyanine green in hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To analyze the influencing factors of abnormal 15-minute retention rate of indocyanine green (ICG R15) (≥10%) in patients with hepatocellular carcinoma, and to construct a nomogram model, and to evaluate the prediction efficiency of the nomogram model.Methods:The clinical data of 190 patients with hepatocellular carcinoma in Zhengzhou University People's Hospital from December 2017 to June 2022 were retrospectively analyzed, including 148 males and 42 females, aged (57.8±9.9) years. According to ICG R15, the patients were divided into ICG R15 normal group ( n=134, ICG R15<10%) and ICG R15 abnormal group ( n=56, ICG R15≥10%). Univariate and multivariate logistic regression were used to analyze the influencing factors of abnormal ICG R15, and the nomogram model was established. The predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and C-index, and the model was verified by calibration curve and decision analysis curve. Results:Abnormal ICG R15 group the proportion of liver cirrhosis, albumin ≤35 g/L, hemoglobin ≤110 g/L, platelet count ≤100×10 9/L, prothrombin time >13 s, alanine aminotransferase >40 U/L, aspartate aminotransferase >40 U/L, total bilirubin >34.2 μmol/L, and the largest tumor diameter >5.0 cm, spleen volume >383.1 cm 3, spleen volume to of non-tumor liver volume (SNLR) >0.276 and liver tumor volume >117.2 cm 3 were higher than that of ICG R15 normal group, and the differences were statistically significant (all P<0.05). Logistic regression analysis showed that liver cirrhosis ( OR=3.89, 95% CI: 1.28-11.80, P=0.016), spleen volume >383.1 cm 3( OR=5.17, 95% CI: 1.38-19.38, P=0.015), SNLR >0.276 ( OR=5.54, 95% CI: 1.44-21.26, P=0.013) and total bilirubin >34.2 μmol/L( OR=10.20, 95% CI: 1.88-55.39, P=0.007) increased the risk of abnormal ICG R15. A nomogram model was constructed based on the above risk factors. The C-index of the model was 0.915 (95% CI: 0.872-0.957), and the area under the ROC curve predicted by the nomogram model was 0.915 (95% CI: 0.871-0.958). The calibration curve showed that the correlation index of the abnormal ICG R15 predicted by the nomogram was similar to actual situation. Decision analysis curve showed high returns. Conclusion:Liver cirrhosis, spleen volume >383.1 cm 3, SNLR>0.276 and total bilirubin >34.2 μmol/L were indepentlent risk factors for abnormal ICG R15 in patients with hepatocellur carcinoma. The clinical prediction model of ICG R15 abnormality constructed by nomogram has good prediction efficiency, which can provide a reference for evaluating preoperative liver reserve function of patients with hepatocellular carcinoma.

Genome characterization and traceability analysis of SARS-CoV-2 in a local outbreak / 中华微生物学和免疫学杂志

Objective:To analyze the genome characteristics and variations in nucleotides and amino acids of SARS-CoV-2 causing an outbreak in Henan Province in November 2021 and perform the traceability analysis.Methods:In this study, throat swab specimens from cases in the acute phase were collected and tested for the nucleic acids of SARS-CoV-2 by real-time fluorescent RT-PCR. SARS-CoV-2 nucleic acid-positive samples were subjected to high-throughput genome sequencing and whole-genome alignment analysis.Results:The median Ct values of ORF1ab gene and N gene in 70 positive specimens was 26.41 (15.58 to 39.27) and 24.43 (12.04 to 39.74), respectively. Compared with the sequence of Wuhan-Hu(NC_045512) reference strain, 47 to 49 nucleotide mutations sharing 47 nucleotide mutation and 41 amino acid mutations were found in 63 strains of successfully sequenced SARS-CoV-2. Nine nucleotide mutations and 12 amino acid mutations were found in the spike protein. The index case shared 47 mutations with the Russian imported cases in Henan Province on October 14 and the local cases in Jiangxi Province in October. Moreover, their genomes were highly homologous and they all belonged to the Delta variant (AY.122 evolutionary branch).Conclusions:Continuous monitoring of imported COVID-19 cases and prolonging the period of quarantine were needed to reduce the risk of local outbreak and epidemic caused by imported COVID-19 cases. Analysis of the genomic characteristics of SARS-CoV-2 and the variations in nucleotides and amino acids was conducive to trace the origin of COVID-19 outbreak quickly and provide reference for precise control.

Childhood onset spinocerebellar ataxia type 2: a family report and literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics, genetic characteristics and diagnosis of spinocerebellar ataxia type 2 (SCA2) patients with childhood onset.Methods:The clinical data of a SCA2 pedigree who diagnosed at Neurogenetic Metabolic Disease Clinic of Children′s Hospital Affiliated to Zhengzhou University in July 2019 were collected, and the reported cases of childhood-onset SCA2 were reviewed. The CAG repeat of ATXN2 gene was detected by polymerase chain reaction, capillary gel electrophoresis and Sanger sequencing techniques.Results:A total of 9 people in 4 generations of the family were affected, showing an autosomal dominant inheritance. The proband was a 3 years and 4 months old boy, who showed abnormal symptoms at 9 months which manifested as developmental retardation. At 1 year old, he developed progressive regression which represented neither to be amused, recognize others, stand and walk alone, nor had language development. Meanwhile, he had difficulty swallowing, long-term constipation, and a history of convulsions. His sister and mother were not yet sick. His grandmother could not walk, had slurred speech accompanied by nystagmus, and magnetic resonance imaging showed cerebellar atrophy. His granduncles and grandaunts had unstable walking and dysarthria. His great-grandfather required wheelchair to walk. This pedigree showed an autosomal dominant inheritance. One of the ATXN2 gene alleles of the proband, his sister, mother and grandmother all showed abnormal amplification with 99, 55, 44, and 43 times respectively and no inserting CAA sequence. A total of 14 literatures reported 20 cases of childhood-onset SCA2 patients who were genetically diagnosed. The majorities had onset in infancy, and few can develop into school age. The main clinical manifestations were developmental delay, dystonia or insufficiency, myoclonus or infantile spasms, motor retardation, abnormal eye movement, retinitis pigmentosa and dysphagia, while the classic cerebellar syndrome was only partially present. Abnormal rhythm was found on electroencephalogram, cerebellar atrophy on magnetic resonance imaging or CT of the head.Conclusions:This case is the youngest genetically-confirmed SCA2 patient reported in China. Reported patients usually have onset in infancy with excessive repeat sequence expansion. Their clinical characteristics are different from the classic patients and could only be diagnosed by dynamic mutation detection.

Application value of peripheral blood circulating tumor cell classification in the prediction of preoperative microvascular invasion of hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the application value of peripheral blood circulating tumor cell (CTC) classification in the prediction of preoperative microvascular invasion of hepato-cellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinico-pathological data of 102 HCC patients who were admitted to Zhengzhou University People's Hospital from September 2018 to September 2020 were collected. There were 71 males and 31 females, aged from 29 to 80 years, with a median age of 57 years. Observation indicators: (1) surgical situations; (2) results of CTC detection and microvascular invasion in HCC patients; (3) results of CTC classification and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC; (4) influencing factors for microvascular invasion in HCC; (5) comparison of clinicopathological features in HCC patients with different cell counts in mesenchymal phenotype of CTC (M-CTC). Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the nonparametric rank sum U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The receiver operating characteristic (ROC) curve was used to determine the best cut-off value for the risk of microvascular invasion in patients. Univariate and multivariate analysis were performed using the Logistic regression model. Results:(1) Surgical situations. All 102 patients underwent surgery successfully, including 17 cases undergoing local hepatectomy, 43 cases under-going segmentectomy, 22 cases undergoing hepatic lobectomy, 13 cases undergoing hemilectomy and 7 cases undergoing enlarged hemilectomy. The operation time and the volume of intraoperative blood loss were 235(147,293)minutes and 300(110,500)mL of the 102 patients, respectively. (2) Results of CTC detection and microvascular invasion in HCC patients. Of 102 patients, there were 36 casas with epithelial phenotype of CTC (E-CTC), 86 cases with hybrid phenotype of CTC (H-CTC), 30 cases with M-CTC, respectively, and the total CTC (T-CTC) were positive in 89 cases. Results of postoperative pathological examination showed that there were 40 cases with micro-vascular inva-sion and 62 cases without microvascular invasion in the 102 patients. Of the 40 patients with micro-vascular invasion, the count of E-CTC, H-CTC, M-CTC and T-CTC were 0(0,1) per 5 mL, 4(2,5) per 5 mL, 1(0,2) per 5 mL and 5(3,8) per 5mL, respectively. The above indicators of the 62 cases without microvascular invasion were 0(0,1) per 5 mL, 3(1,5) per 5 mL, 0(0,0) per 5 mL and 3(2,6) per 5 mL, respectively. There were significant differences in the count of M-CTC and T-CTC between patients with and without microvascular invasion ( Z=-4.83, -2.96, P<0.05). (3) Results of CTC classi-fication and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC. The ROC curve showed that best cut-off value of M-CTC and T-CTC counts in the prediction of microvascular invasion in HCC were 1 per 5 mL and 4 per 5 mL, respectively, with the area under curve, the corresponding specificity, sensitivity were 0.70 (95% confidence interval as 0.60-0.81, P<0.05), 75.8%, 62.9% and 0.67 (95% confidence interval as 0.57-0.78, P<0.05), 60.0%, 72.5%, respec-tively. (4) Influencing factors for microvascular invasion in HCC. Result of univariate analysis showed that alpha fetoprotein (AFP), aspartate aminotransferase (AST), tumor diameter, tumor number, tumor margin, Barcelona clinic liver cancer staging, M-CTC counts and T-CTC counts were related factors influencing microvascular invasion in HCC ( odds ratio=3.13, 0.43, 4.92, 5.65, 2.54, 2.93, 8.25, 4.47, 95% confidence interval as 1.34-7.33, 0.19-0.98, 2.09-11.58, 2.35-13.63, 1.13-5.75, 1.27-6.74, 3.13-21.75, 1.88-10.61, P<0.05). Result of multivariate analysis showed that tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL were independent risk factors influencing microvascular invasion in HCC ( odds ratio=2.97, 4.14, 4.36, 95% c onfidence interval as 1.01-8.70, 1.14-15.02, 1.36-13.97, P<0.05). (5) Comparison of clinicopathological features in HCC patients with different cell counts in M-CTC. The 102 HCC patients were divided into the high M-CTC group of 30 cases with M-CTC counts ≥1 per 5 mL and the low M-CTC group of 72 cases with M-CTC counts <1 per 5 mL, according to the best cut-off value of M-CTC counts. Cases with hepatitis, cases with AFP >400 μg/L, cases with AST >35 U/L, cases with irregular tumor margin, cases with tumor diameter >5 cm, cases with tumor number as multiple and cases with micro-vascular invasion were 22, 17, 13, 21, 18, 16 and 22 in the high M-CTC group of 30 cases. The above indicators were 35, 18, 48, 26, 25, 21 and 18 in the low M-CTC group of 72 cases. There were significant differences in the above indicators between the high M-CTC group and the low M-CTC group ( χ2=5.25, 9.42, 4.80, 9.79, 5.55, 5.35, 20.75, P<0.05). Conclusions:The epithelial-mesen-chymal phenotype of peripheral blood CTC can be used to predict the preoperative microvascular invasion in HCC. Tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL are independent risk factors influencing microvascular invasion in HCC patients.

Clinical characteristics and literature review of a case of Christianson syndrome caused by SLC9A6 gene variation / 中华神经科杂志

Objective:To retrospectively analyze the clinical data of Christianson syndrome caused by SLC9A6 gene mutation and related literatures.Methods:The clinical data of one Christianson syndrome patient caused by SLC9A6 gene variation in Children′s Hospital of Zhengzhou University were collected, meanwhile the relevant literature was reviewed. The examination of video electroencephalogram, auditory brainstem response, and cranial magnetic resonance imaging (MRI) was performed. Whole exon sequencing and mitochondrial gene detection were performed for 3 persons in the family, and the suspected mutation sites were verified by Sanger sequencing.Results:A boy, 7 years old, presented with epilepsy, language retardation and mental retardation. Now he can only say overlapping words, execute simple instructions, denying family history of genetic disease and genetic metabolic disease. The patient′s uncle had the history of febrile convulsions in childhood. At present, speech and intelligence are impaired, and the left limb movement is slightly limited. The patient′s mother was mildly retarded, without epilepsy. The video- electroencephalogram of the patient was shown below (April 2021): abnormal electroencephalogram; background activity was slightly slow; the bilateral frontotemporal region was dominated by multi-focal spiky wave, spiky slow wave and slow wave in each waking and sleeping stage, which can be generalized and extensive; in the sleeping stage, the discharge index in non-rapid eye movement stage was about 75%. The auditory brainstem response was shown below (October 2021): the left 70 dB Ⅰwave latency was prolonged; the Ⅰwave Ⅴ wave shape was poor; the threshold was 20 dB (the high frequency threshold was normal); the right 70 dB Ⅰwave latency was prolonged; the wave form was poor; the amplitude was lower than that of the contralateral side; Ⅲ wave Ⅴ wave shape was poor; the threshold was 30 dB (the high frequency threshold slightly increased). Brain MRI thin-section scan was shown below (January 2021): subarachnoid space of bilateral temporal poles widened, and no obvious abnormal signal was found in brain parenchyma; sinusitis. Whole exome sequencing of 3 persons in the family indicated that the proband had a hemizygous variant c.616C>T (p.R206 *) in the SLC9A6 gene. Using the SLC9A6 gene and Christianson syndrome as the key words, 94 foreign literatures from January 1989 to January 2022 were researched. Totally, 81 Christianson syndrome patients caused by SLC9A6 gene mutation were reported. The age of onset ranged from neonatal period to adulthood, and the clinical manifestations were heterogeneous. The symptoms of male patients mainly included epilepsy, severe cognitive impairment, ataxia, cerebellar atrophy, and psychomotor retardation. Conclusions:The hemizygous variant of SLC9A6 gene (c.616C>T) is the etiology of this patient. The possibility of Christianson syndrome shall be considered for recurrent epilepsy with poor efficacy of antiepileptic drugs, status epilepticus during slow-wave sleep, and delayed development of motor intelligence. Genetic testing is helpful for definite diagnosis and treatment.

Analysis of the dynamic changes of serum IgM and IgG antibodies of the COVID-19 patients / 中华微生物学和免疫学杂志

Objective:To monitor the changes in specific IgM and IgG antibodies in patients diagnosed with COVID-19 after SARS-CoV-2 infection, and analyze their clinical significance.Methods:A total of 168 serum samples were collected from 56 COVID-19 patients with different disease courses who were positive for nucleic acid test at Henan Center for Disease Control and Prevention on January 8, 2020 and February 21, 2020. Serum samples from 25 healthy people excluded from COVID-19 were used as control group. IgM and IgG antibodies against SARS-CoV-2 were detected by chemiluminescence method.Results:IgM antibody increased sharply in 1-3 weeks after onset, and reached the peak value (21.78 AU/ml) in the 3rd week after onset. IgG antibody increased the most in 3-6 weeks after onset, and reached the peak value (81.58 AU/ml) in the 9th week after onset. The levels of IgM and IgG antibodies were closely correlated with age and disease course ( P<0.05). The antibody level of 30-60 years old group was the highest, the IgM antibody positive rate and antibody level of acute stage and previous infection were lower than that of recovery stage, and the IgG antibody positive rate and antibody level of acute stage were lower than that of recovery stage and previous infection. During the whole course of the disease, the levels of IgM and IgG antibodies increased gradually in the acute stage, reached the peak in the recovery stage, and decreased and maintained at a certain level in the past infection. Conclusions:Serum SARS-CoV-2 IgM and IgG antibody detection can be used as auxiliary diagnostic indicators for COVID-19, and its continuous observation is helpful for epidemiological investigation, serological diagnosis and disease course monitoring.

Genomic characteristics of 2019 novel coronavirus from imported cases of coronavirus disease 2019 in Henan Province / 中华传染病杂志

Objective:To analyze the evolutionary characteristics and variations of 2019 novel coronavirus (2019-nCoV) strains imported from abroad in Henan Province.Methods:A total of 16 imported cases of coronavirus disease 2019 (COVID-19) reported in Henan Province from May to December 2020 were enrolled. The throat swab specimens from the patients were collected and sent to the Henan Provincial Center for Disease Control and Prevention for whole genome sequencing. Taking SARS-CoV-2 Wuhan-Hu-1 published in Global Initiative on Sharing All Influenza Data (GISAID) as the reference sequence, the sequences were aligned and analyzed by MEGA X, and the phylogenetic tree was constructed by the maximum likelihood method.Results:Among 16 cases, 13 cases were imported from Russia, two cases were imported from Myanmar, and one case was imported from Ukraine. A total of 16 strains of 2019-nCoV genomes with the lengths of 29 804 bp to 29 882 bp were obtained. A total of 145 nucleotide mutations and 80 amino acid mutations were detected. Nucleotide variations of C241T, C3037T, C14408T, A23403G and the amino acid variation of D614G in spike protein were detected in all sequences. Meanwhile, insertion A at the site of 29704 was found in BetaCov/HEN02/Human/2020, BetaCov/HEN04/Human/2020 and BetaCov/HEN05/Human/2020. Deletion variation was not found. Phylogenetic analysis showed that there was no correlation between the 16 strains and currently epidemic variants of concern (VOC) .Conclusion:From May to December 2020, the detection of viral genome mutations in the imported cases of Henan Province shows randomness and diversity, while the strains are not VOC.

Analysis of the local dengue fever outbreak in the north of Henan Province in 2019 / 中华微生物学和免疫学杂志

Objective:To provide data support for the prevention and control of dengue fever in Henan Province by analyzing the molecular epidemiological and etiological characteristics of dengue fever outbreaks in Puyang in 2019.Methods:Blood samples were collected from all suspected cases of dengue fever. The antigen, antibody and nucleic acid of dengue virus (DENV) were detected. The E gene was amplified by viral nucleic acid extraction and sequenced. Phylogenetic tree was constructed to trace the source of infection. Results:A total of 61 local cases of dengue fever were reported, and no deaths were reported. Among them, 4 cases (72.13%) were positive for DENV NS1 antigen; 16(26.23%) cases were positive for specific IgM; 38(62.30%) cases were positive for specific IgG; 34 cases (54.10%) were positive for dengue nucleic acid testing. Ten dengue virus strains were isolated, all of which were dengue virus type 1(DENV-1). Sequence analysis of E gene suggested it belonged to the same clade as Henan201903 strain imported from Cambodia to Zhumadian, Henan in 2019, with the highest homology. Conclusions:The dengue fever epidemic in Henan Province was caused by DENV-1, which might be improted from Cambodia, Singapore, Myanmar and other Southeast Asian countries. Therefore, the surveillance of DENV in people returning from Southeast Asia should be strengthened.

3-Hydroxy-isobutyryl-coenzyme A hydrolase deficiency: a case report and literature review / 中华神经科杂志

Objective:To analyze the characteristics of clinical manifestation, auxiliary examination and gene mutation of 3-hydroxy-isobutyryl-coenzyme A hydrolase (HIBCH) deficiency to better understand this disease.Methods:The clinical manifestations and genetic results of a patient with HIBCH deficiency were analyzed. The clinical features and genetic characteristics of HIBCH deficiency were summarized based on the literature review.Results:The proband, female, one year and four months old, was admitted to Children′s Hospital Affiliated to Zhengzhou University for “vomiting and diarrhea for 15 days, dyspnea and intermittent convulsions for 13 days after digestive tract infection”. The intelligence was normal, however, the motor development was slightly delayed before onset. Physical examination showed light coma, poor response and insensitivity to light. She also had shortness of breath, weak positive three concave signs and coarse breath sound in both lungs with sputum purrs. In addition, the muscle tension of extremities was increased. Bilateral Brudzinski′s sign, Babinski′s sign and Kernig′s sign were negative. Serum hydroxybutyryl carnitine (C4OH) was increased. Cranial magnetic resonance imaging (MRI) showed atrophy in bilateral cerebral hemispheres and abnormal symmetry signals in bilateral globus pallidus and cerebral peduncle. Novel compound heterozygous variants of HIBCH, c.489T>A (p. C163*) and c.740A>G (p. Y247C), were found in the patient, which respectively inherited from her healthy parents. Her symptoms were relieved after“cocktail”therapy and symptomatic treatment. Literature related to HIBCH deficiency published all around the world was reviewed. As a result, 17 articles, including 24 cases, had been reported. The majority of patients presented with poor feeding, dystonia and progressive motor developmental delay in early infancy. Cranial MRI showed lesions in bilateral basal ganglia. Serum C4OH concentration was elevated. And compound heterozygous or homozygous variants of HIBCH gene were found in patients with HIBCH deficiency.Conclusions:The detection of serum amino acids and acylcarnitine profiles on HIBCH deficiency was relatively specific and it was helpful to make a clear diagnosis by combining with cranial MRI and genetic tests. In this study, a case of HIBCH deficiency was confirmed, which expanded the mutation spectrum of HIBCH gene. Meanwhile, summarizing the clinical and genetic characteristics of cases reported improved understanding of HIBCH deficiency.

Clinical and genetic analysis of a child with 2q37 deletion syndrome resulting from a translocation involving chromosome satellite / 中华医学遗传学杂志

OBJECTIVE@#To carry out cyto- and molecular genetic testing for a child featuring facial dysmorphism and attention deficit and hyperactive disorder.@*METHODS@#The child was subjected to routine peripheral blood lymphocyte chromosomal karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) analyses.@*RESULTS@#The child's facial dysmorphism included low-set ears, curly ear auricle, protuberance of eyebrow arch, nostril notch, short and flat philtrum and thin upper lip. SNP-array revealed that he has carried a 4.883 Mb deletion at 2q37. His chromosomal karyotype was ultimately determined as 45, XY, der(2;21) (2pter→ 2q37.3::21p13→ 21p10::20p10→ 20pter), der(20) (21qter→ 21q10::20q10→ 20qter).@*CONCLUSION@#A rare case of 2q37 deletion syndrome involving three chromosomes was discovered. Combined use of various cyto- and molecular genetic techniques is crucial for the diagnosis of chromosomal abnormalities with complex structures.

Clinical and molecular genetic analysis of a case of MEGDEL syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a child with MEGDEL syndrome.@*METHODS@#Clinical data of the child was reviewed. Peripheral blood samples of the child and his parents were collected. Mitochondrial genome and the whole exome of the child were analyzed by next-generation sequencing. Candidate variants and its origin were verified by Sanger sequencing and fluorescence quantitative PCR.@*RESULTS@#The patient, a 2-year-and-6-month-old male, has featured hypoglycemia, mental and motor retardation with regression. Cranial MRI showed bilateral putamen damage suggestive of Leigh syndrome. Testing of urine organic acid indicated that the level of 3-methylpentenoic acid was slightly increased. Whole exome sequencing revealed that the child has harbored heterozygous deletion of exons 6 to 17 and c.307A>T nonsense variant of the SERAC1 gene, which were respectively inherited from his parents who were asymptomatic. Treatment with Levocarnitine, vitamin B1, vitamin B2, coenzyme Q10, baclofen and glucuronolactone resulted in improvement of sleep and mental state.@*CONCLUSION@#A case of MEGDEL syndrome without deafness was diagnosed. Discovery of the nonsense mutation and large fragment deletion have enriched the spectrum of SERAC1 gene variants.

Phenotypic and genetic analysis of a case with hypohidrotic ectodermal dysplasia due to Xq13.1 microdeletion / 中华医学遗传学杂志

OBJECTIVE@#To investigate the clinical phenotype and genetic characteristics of a patient with hypohidrotic ectodermal dysplasia (HED) due to partial deletion of EDA gene.@*METHODS@#The child has presented with HED complicated with epilepsy. Family trio whole exome sequencing (Trio-WES), copy number variation sequencing (CNV-seq), and karyotype analysis were carried out to explore the underlying genetic etiology.@*RESULTS@#The proband, a 7-year-and-8-month-old boy, presented with thin curly hair, thin and sparse eyebrow, xerosis cutis, susceptibility to hyperthermia from childhood, hypohidrosis, sharp/sparse/absent teeth, saddle nose, prominent forehead, auricle adulation and seizure. He was found to have a normal chromosomal karyotype, and no abnormality was found by Trio-WES. Genome-wide CNV-seq revealed a 341.90 kb deletion at Xq13.1q13.1 (chrX: 68 796 566-69 138 468). As verified by PCR-electrophoresis, the deletion has removed part of the EDA gene. The deletion was derived from his mother with normal hair, mild xerosis cutis, and sparse, decidulated and nail-like teeth. The mother was detected with a heterozygous 242.10 kb deletion at Xq13.1q13.1 (chrX: 68 836 154-69 078 250).@*CONCLUSION@#Both the proband and his mother have carried a Xq13.1 microdeletion involving part of the EDA gene. The clinical phenotypes of the mother and the proband were consistent with the clinical characteristics of X-linked recessive HED, for which partial deletion of the EDA gene is probably accountable.

Case report of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency / 中华实用儿科临床杂志

A case with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency(HMGCSD)was related and foreign and domestic reported cases were reviewed.The female proband was 7 months and 16 days old, and admitted to the hospital due to acute onset of " fever for 4 days, wheezing for 3 hours, dyspnea and moaning for 2 hours" . She was mainly manifested as encephalopathy, hepatomegaly, liver function damage, low ketone hypoglycemia, and hyperlipidemia.She died of respiratory and circulatory failure on the third day of hospitalization.Two compound he-terozygous variants in HMGCS2 gene were found by total exome sequencing, namely, c.1061+ 1 G> C and c. 476 G> T. HMGCSD could be diagnosed by gene detection in combination with clinical features of the patient. Thirteen literatures related to HMGCSD were collected, including 26 patients in total, with the age of onset ranging from 3 months to 6 years. The main cause of the disease was insufficient intake, mainly manifested as hypoglycemia accompanied by low ketone, hepatomegaly, liver damage, etc. A high level of urinary 4- hydroxy-6- methyl-2- pyrone might be a strong indicator of HMGCSD. Three died during the acute attack. Up to now, there were 32 mutations in HMGCS2 reported in 26 patients, and the main type was missense mutation. In this article, the second case of HMGCSD in China was identified, and 2 novel variants of HMGCS2 were found, which extended the clinical phenotype and mutation spectrum of HMGCSD.

Study of clinical characteristics and related gene mutations in children with hereditary spherocytosis / 中华实用儿科临床杂志

Objective:To analyze the clinical phenotypes and molecular genetic characteristics of hereditary spherocytosis (HS) in children.Methods:The clinical data of children with HS in the Affiliated Children′s Hospital of Zhengzhou University from June 2014 to June 2018 were collected and analyzed retrospectively.The peripheral blood samples of 20 children and their parents were collected and targeted capture or whole exon group sequencing was performed using the second generation sequencing technique, and the suspicious mutation sites were verified by Sanger sequencing.Results:A total of 43 pediatric patients (23 males, 20 female) were included in this study.The median age of onset of 1 year old and 11 months (1 month to 10 years old). Pallor (27/43 cases, 62.79%) was the main symptom.Typical clinical manifestations were anemia (36/43 cases, 83.72%), jaundice (35/43 cases, 81.40%), splenomegaly (33/43 cases, 76.74%), and hepatomegaly (27/43 cases, 62.79%). The proportion of spherical erythrocytes in peripheral blood of 23 cases (23/43 cases, 53.49%)≥ 0.1, and the proportion of spherical erythrocytes in bone marrow smears of 17 cases (39.53%) was ≥ 0.1, and 20 cases were positive in erythrocyte osmotic fragility test (20/43 cases, 46.51%). Comparison of 29 children before and after blood transfusion: post-transfusion hemoglobin (Hb) [(88.69±11.22) g/L vs. (78.24±14.47) g/L], mean corpuscular volume (MCV) [(89.37±7.15) fL vs.(84.08±7.49) fL], mean corpuscular hemoglobin (MCH) [(29.12±2.70) pg vs.(27.36±1.95) pg], mean corpuscular hemoglobin corpuscular (MCHC) [(361.79±32.27) g/L vs.(356.31±31.43 ) g/L] were increased, and the total bilirubin (TB) level was lower after blood transfusion than before blood transfusion [(33.27±16.42) μmol/L vs.(41.58±15.40) μmol/L], the differences were statistically significant ( t=-3.538, -5.187, -5.412, -7.404, 2.527, all P<0.05). Seven children underwent splenectomy: postoperative Hb[(116.00±5.54) g/L vs.(75.71±9.96) g/L], MCH[(29.87±1.62) pg vs.(24.61±1.65) pg], MCHC [(391.14±12.99) g/L vs.(315.14±51.99) g/L] all increased, the difference was statistically significant ( t=-9.234, -4.330, -4.031, all P<0.05). The Hb in the operation group was significantly higher than that in the blood transfusion group, including the treatment effect of operation was more significant ( t=-9.247, P<0.05). Thirteen pathogenic mutations (11 new mutations not reported) were detected in 3 genes ( ANK1, SPTB and SPTA1) in 13 children, 8 of who were mutations in ANK1, 4 cases of which were mutations in SPTB and 1 case of which was mutation in SPTA1.Among the 13 mutations, 12 cases were de novo except one inherited from the mother. Conclusions:Anemia and pallor are the initial symptoms of HS in children.Blood transfusion can temporarily improve the symptoms of anemia and jaundice.Splenectomy is an effective and fundamental treatment.The gene diagnosis of 13 pediatric patients got gene diagnosis, which provided basis for genetic consultation of the next fetus.Eleven new mutations were found in ANK1, SPTB, SPTA1 genes, which exten-ded the gene mutation spectrum of HS.

Phenotypic and genetic analysis of a boy with partial trisomy of 22q / 中华医学遗传学杂志

OBJECTIVE@#To delineate the nature and origin of chromosomal aberration in a boy with mental retardation and multiple congenital deformities.@*METHODS@#Chromosomal karyotypes of the proband and his parents were determined by routine G-banding analysis. Genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).@*RESULTS@#The karyotype of the proband was 46,X,add(Y)(q11.23). No karyotypic abnormality was detected in either parent. SNP array has identified a de novo 21.6 Mb duplication at 22q12qter in the proband.@*CONCLUSION@#The de novo 22q12qter duplication probably underlies the abnormalities in the proband.