Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

OBJECTIVE To investigate the anti-inflammatory effects and mechanism of Zhuang medicine Tongfeng li’an capsules on gouty arthritis in combination with in vivo and in vitro experiments. METHODS Sixty rats were randomly divided into normal group， model group， positive control group （27 mg/kg allopurinol+0.27 mg/kg colchicine）， Tongfeng li’an capsules low- dose， medium-dose and high-dose groups （2.2， 4.5， 9.0 g/kg）， with 10 rats in each group. Except for normal group， gouty arthritis model of rats was induced in other groups. Rats in each administration group were given corresponding drugs intragastrically， and rats in the normal group and model group were given equal volume of water intragastrically for 14 consecutive days. The degree of ankle joint swelling， serum level of interleukin-1β （IL-1β） and protein expressions of nuclear factor kappa-B （NF-κB） in synovial tissue were detected， and the histopathological changes of synovium tissue in the ankle joint of rats were observed. The inflammation model was established by stimulating RAW264.7 cells with lipopolysaccharide. After Tongfeng li’an capsules （62.5， 125， 250 μg/mL） were given， the levels of nitric oxide （NO）， reactive oxygen species （ROS） and IL-1β in the cells and protein expression of NF-κB were detected， and NF-κB localization in the cells was also determined. RESULTS Results of in vivo experiment showed that compared with normal group， the swelling degree of the ankle joint， serum IL-1β level and protein expression of NF-κB in synovium tissue were all increased significantly in model group （P＜0.05）； pathological changes such as synovial hyperplasia， edema， vascular congestion， capillary hyperplasia， and increased inflammatory cells were observed. Compared with model group， the levels of above indexes were all decreased significantly in Tongfeng li’an capsules high-dose group （P＜0.05）， and most of the above indexes were significantly reduced in Tongfeng li’an capsules medium-dose and low-dose groups （P＜0.05）； synovial hyperplasia of the ankle joint improved， and the infiltration of inflammatory cells 2019BS044） decreased. Results of in vitro experiment showed that Tongfeng li’an capsule could significantly reduce the levels of NO， ROS and IL-1β and protein expression of NF-κB（P＜0.01）， and inhibit NF- κB nucleation. CONCLUSIONS Tongfeng li’ancapsules have good anti-inflammatory effect on gouty arthritis， and its mechanism may be related to the inhibition of NF-κB signaling pathway activity.

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation, language delay and autism. METHODS: G-banding chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were carried out for the child and her parents. RESULTS: The child was found to have a 46,XX,dup(8p?) karyotype, for which both of her parents were normal. SNP-array revealed that the child has harbored a 6.8 Mb deletion in 8p23.3p23.1 and a 21.8 Mb duplication in 8p23.1p12, both of which were verified as de novo pathogenic copy number variants. CONCLUSION The clinical features of the child may be attributed to the 8p deletion and duplication. SNP-array can facilitate genetic diagnosis for children featuring mental retardation in conjunct with other developmental anomalies.
Humans ; Child ; Pregnancy ; Female ; Intellectual Disability/genetics* ; Prenatal Diagnosis ; Karyotyping ; Chromosome Banding ; Chromosome Deletion

We reported a fetus with limb abnormalities and abnormal ultrasound soft markers diagnosed with nemaline myopathy. A pregnant woman (G1P0) underwent amniocentesis at 18 +2 gestational weeks due to thickened nuchal translucency suggested by ultrasound at 13 +5 gestational weeks. Karyotyping and single nucleotide polymorphism array of the amniotic fluid cells showed no fetal abnormalities. However, ultrasonographic reexaminations at 23, 28, and 28 +1 weeks indicated limb abnormalities and thickened nuchal fold, and the pregnant woman chose to terminate the pregnancy at 29 +2 gestational weeks. Whole exome sequencing showed compound heterozygous mutations of c.602G>A (p.W201*) and c.1516A>C (p.T506P) in the KLHL40 gene inherited from the mother and the father, respectively, resulting in nemaline myopathy type 8.

OBJECTIVE: To assess the application value of combined detection of HbA2 and HbF for the screening of thalassemia among a population of childbearing age in Quanzhou, Fujian, and determine the optimal cut-off values for the region. METHODS: Capillary hemoglobin electrophoresis and genetic testing for α and β globin gene mutations were simultaneously carried out on 11 428 patients with suspected thalassemia. Statistical methods were used to analyze the distribution of various types of thalassemia and compare the performance of HbA2 and HbF measurement for the screening of various types of thalassemia. The optimal cut-off values for HbA2 and HbF were determined with the ROC curves. RESULTS: 4591 patients with α, β, and αβ compound thalassemia were identified by genetic testing. The most common genotypes for α and β thalassemia included --SEA/αα and β654/βN, β41-42/βN, and β17/βN. The ROC curves were drawn to compare the performance of HbA2 screening for α-, β-, αβ-compound, static α-, mild α-, and intermediate α-thalassemia, and the maximum area under the curves was 0.674, 0.984, 0.936, 0.499, 0.731, 0.956, and the optimal cut-off values for HbA2 were 2.45%, 3.25%, 3.65%, 2.95%, 2.55%, 1.75%, respectively. CONCLUSION HbA2 is an efficient indicator for identifying intermediate types of α-, β-, and αβ compound thalassemia. The combination of HbA2 and HbF measurement can effectively detect carriers for β-thalassemia mutations.
Genotype ; Hemoglobin A2/genetics* ; Heterozygote ; Humans ; Mass Screening ; Mutation ; alpha-Thalassemia ; beta-Thalassemia/genetics*

OBJECTIVE: To explore the genetic etiology of spontaneous abortions by using chromosomal microarray analysis (CMA). METHODS: Fetal tissues derived from 106 spontaneous abortion samples were subjected to CMA assay to detect genome copy number variants (CNVs). RESULTS: The test was successful in 94 cases (88.68%). Fifty four chromosomal abnormalities were detected, which included 44 numerical chromosomal aberrations mainly consisting of aneuploidies, triploidies and mosaicisms. Four pathogenic CNVs were detected, and two of which involved the Cri-du-chat syndrome regions. In addition, 6 chromosomal mosaicism were detected. CONCLUSION Numerical chromosomal aberrations and CNVs are the main causes for early spontaneous abortions. CMA can effectively reveal the genetic etiology of spontaneous abortions. Spontaneous abortions at gestational weeks 10 to 11⁺⁶ has the highest rate for chromosomal abnormalities, which may provide valuable information for clinical counseling.
Abortion, Spontaneous/genetics* ; Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Humans ; Microarray Analysis ; Mosaicism ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic etiology for a patient featuring intellectual disability and torticollis. METHODS: Peripheral blood sample was collected from the patient and subjected to G-banded karyotyping analysis and single nucleotide polymorphism array (SNP-array) assay. RESULTS: The patient was found to have a chromosomal karyotype of 46,XX. SNP-array revealed that she has harbored a 3.8 Mb microdeletion at 10q26.3 which has encompassed 21 OMIM genes including EBF3 and ECHS1, and a 7.3 Mb duplication at 18q22.3q23 which has encompassed 19 OMIM genes including TSHZ1 and TXNL4A. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 10q26.3 deletion was predicted to be pathogenic, whilst the 18q22.3q23 duplication was predicted to be variation of unknown significance. CONCLUSION The clinical phenotype of the patient may be mainly attributed to the 10q26.3 microdeletion, and haploinsufficiency of the EBF3 gene may account for her intellectual deficiency. Above finding has provided a basis for genetic counseling for the patient.
Female ; Animals ; Genetic Testing ; Genetic Counseling ; Karyotyping ; Chromosome Banding ; Genomics

OBJECTIVE: To apply combined non-invasive prenatal testing (NIPT), chromosomal karyotyping and chromosomal microarray for the screening and prenatal diagnosis of a fetus with supernumerary small marker chromosome (sSMC). METHODS: Standard NIFTY and full gene NIFTY kits were applied to detect free DNA (cfDNA) isolated from peripheral blood sample of a pregnancy woman. Amniocentesis was carried out for the woman for an abnormal NIPT result. G-banded karyotyping and single nucleotide polymorphism array (SNP array) were used to determine the karyotype and copy number variants in the fetus. The result was validated with a fluorescence in situ hybridization (FISH) assay. RESULTS: Both the standard NIFTY and full gene NIFTY indicated abnormal dup(chr12:707 334-33 308 759), for which the T score value of copy number anomaly in full gene NIFTY is 6.823, which is higher than the standard NIFTY's T-score value of 3.9535. The two NIFTY results were both above the normal threshold ± 3. Conventional G-banding analysis of amniocytes showed that the fetus has a karyotype of 47,XY,+mar. SNP-array delineated duplication of 12p (arr [hg19]12p13.33p11.1 (173 786_34 385 641)× 4, which was verified by FISH. Based on the above results, the fetus was diagnosed as a novel case of Pallister-Killian syndrome. CONCLUSION NIPT has a certain value for the prenatal detection of PKS. Combined use of multiple techniques can facilitate delineation of the source of sSMC.
Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 12/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy

OBJECTIVE: To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS). METHODS: Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child. RESULTS: The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C.3500T>C (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3. CONCLUSION The novel c.3500T>C (p.Ile1167Thr) missense mutation of the SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.
Cell Cycle Proteins/genetics* ; Child ; DNA Copy Number Variations ; De Lange Syndrome/genetics* ; Humans ; Infant, Newborn ; Mutation ; Phenotype ; Whole Exome Sequencing

Objective: To explore the genetic basis of a child with developmental delay and intellectual disability. Methods: Peripheral blood samples of the child and his parents were collected for routine G-band karyotyping analysis and single nucleotide polymorphism array (SNP array) assay. Amniotic fluid sample was collected during the next pregnancy for prenatal diagnosis. Results: No karyotypic abnormality was found in the child and his parents. SNP array showed that the child has carried a 855.3 kb microduplication in 15q11.2. His mother carried the same duplication but had no phenotypic anomaly. No microdeletion/microduplication was found in his father. Upon prenatal diagnosis, no abnormalities was found with the chromosomal karyotype and SNP array result of the fetus. Conclusion 15q11.2 microduplication may result in developmental delay and intellectual disability, for which CYFIP1 may be a candidate gene. However, the duplication may increase the risk but with a low penetrance. This should attract attention during clinical consultation.