Clinical characteristics and genetic analysis of two children with Tuberous sclerosis complex / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC).@*METHODS@#Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members.@*RESULTS@#Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS).@*METHODS@#A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed.@*RESULTS@#The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

Application of fluorescence in situ hybridization combined with chromosomal karyotyping analysis in children with disorders of sex development due to sex chromosome abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD).@*METHODS@#A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children.@*RESULTS@#In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation.@*CONCLUSION@#Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.

Role of thromboelastography in assessing the risk of spontaneous bleeding in patients with liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the association between thromboelastography (TEG) parameters and bleeding in patients with liver cirrhosis and whether TEG can be used to predict the risk of spontaneous bleeding in patients with liver cirrhosis, and to provide a basis for its preventive treatment. MethodsA retrospective analysis was performed for the clinical data of 174 patients with liver cirrhosis who attended Huadu People’s Hospital from May 2018 to April 2020 and did not receive invasive procedure, and according to the condition of bleeding, they were divided into non-bleeding group(n=64), gastrointestinal bleeding group(n=61), and mucocutaneous/oronasal bleeding group(n=49). The medical record system and laboratory information system were used to collect related information and laboratory test results for statistical analysis. The t-test was used for comparison of normally distributed continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. MedCalc software was used for receiver operating characteristic (ROC) curve analysis, and the area under the ROC curve (AUC) was calculated for commonly used coagulation markers and TEG parameters in predicting the risk of bleeding in patients with liver cirrhosis. Cut-off value, sensitivity, specificity, positive predictive value, and negative predictive value were determined, and the Z test was used for comparison of indices in predicting mucocutaneous/oronasal bleeding. ResultsOf all 174 patients, 110 (63.2%) experienced spontaneous bleeding, among whom 61 (55.5%) had gastrointestinal bleeding and 49 (44.5%) had mucocutaneous/oronasal bleeding. There were significant differences in maximum amplitude (MA) and K between the bleeding group and the non-bleeding group (t=2.241 and -2.605, both P＜0.05). There were significant differences between the mucocutaneous/oronasal bleeding group and the non-bleeding/gastrointestinal bleeding groups in platelet count (PLT) and the TEG parameters of clot formation time, a-angle, MA, and coagulation index (CI) (F=3.947, H=12.867, F=4.007, F=8.498, F=5.420, all P＜0.05). Among the TEG parameters, reaction time and Lys30 were generally within the normal range, while there was a prolonged kinetics (K) time and reductions in a-angle, MA, and CI. PLT ≤40×109/L, MA ≤357 mm, K time ＞4.2 minutes, a-angle ≤51.6, and CI ≤-5.9 could be used to predict spontaneous mucocutaneous/oronasal bleeding in patients with liver cirrhosis (all AUC ＞0.7), with positive predictive values of 82.4, 88.9, 81.0, 72.7, and 73.7, respectively, and negative predictive values of 68.3, 72.5, 73.0, 69.4, and 66.7, respectively. ConclusionPLT and the TEG parameters of K time, a-angle, MA, and CI can predict spontaneous bleeding caused by abnormal coagulation in liver cirrhosis, while conventional coagulation parameters prothrombin time and activated partial thromboplastin time cannot predict such bleeding, which provides a basis for the treatment of coagulation disorder and transfusion of blood components for patients with liver cirrhosis.

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.

The value of detecting MLL gene rearrangement in children with acute monocytic leukemia / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of detecting the rearrangement of mixed lineage leukemia (MLL) gene in children with acute mononuclear leukemia (AML).@*METHODS@#Dual-color fluorescence in situ hybridization (FISH) probe was used to detect MLL gene rearrangement in 68 children with AML by interphase FISH. The results were compared with that of conventional G banding chromosomal analysis.@*RESULTS@#Among the 68 children, 28 were detected by FISH with positive hybridization signals, with a detection rate for MLL gene rearrangement being 41.2%. Twelve (17.6%) reciprocal translocations and interruption of 11q23 were detected by G banding analysis. The difference in the detection rates between the two methods was statistically significant (P< 0.05).@*CONCLUSION@#The sensitivity of FISH assay for MLL gene rearrangement was significantly higher than that of G banding chromosomal karyotyping. Combined use of both methods for children with AML can improve the detection rate of MLL gene rearrangements and provide crucial clues for clinical diagnosis, treatment and prognosis.