OBJECTIVES: To explore the value of ferroptose-related genes in the diagnosis and prediction of ulcerative colitis (UC). METHODS: We used UC dataset from the GEO database to screen for differentially expressed genes (DEGs) in UC. The DEGs related to ferroptositis were screened from the FerrDb database and their functions were analyzed. The hub genes were identified by constructing the protein-protein interaction network (PPI), the differences in immune infiltration levels between UC and the control group were evaluated using CIBERSORT, and the diagnostic values of the hub genes for UC were verified by using the training set. In a mouse model of UC, we examined the expression levels of the hub genes in the colon tissues of the mice using real-time fluorescence quantitative PCR (qPCR). RESULTS: We identified a total of 76 DEGs related to ferroptosis. Functional enrichment analysis showed that these genes were significantly enriched in ferroptosis and hypoxia pathways. The PPI network identified 10 hub genes, and 9 of them were highly expressed in UC. Analysis of immune cell infiltration showed that 27 cell types were significantly increased in UC (P<0.05), and the immune checkpoints-related genes had the strongest correlation with the hub gene PPARG (P<0.05). Verification analysis using the training set showed that P4HB, PPARG and STAT3 had the best predictive value for UC (P<0.05). In the UC mouse model, the expression of PPARG was significantly decreased and the expressions of P4HB and STAT3 were significantly increased in the colon tissues of the mice as compared with the normal mice. CONCLUSIONS Ferroptose-related genes have significant value for diagnosis and prediction of UC.
Colitis, Ulcerative/genetics* ; Animals ; Mice ; Ferroptosis/genetics* ; Humans ; Protein Interaction Maps ; Disease Models, Animal ; Gene Expression Profiling ; STAT3 Transcription Factor/genetics*

OBJECTIVE: To explore the clinical features and genetic etiology of two children with intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia (MICPCH). METHODS: Two children with MICPCH who were presented at the Henan Provincial People's Hospital between April 2019 and December 2021 were selected as the study subjects. Clinical data of the two children were collected, along with peripheral venous blood samples of them and their parents, and amniotic fluid sample of the mother of child 1. Whole exome sequencing (WES), array-comparative genomic hybridization (aCGH) and real-time quantitative PCR (qPCR) were carried out for the children, their parents and the fetus. The pathogenicity of candidate variants were evaluated. RESULTS: Child 1 was a 6-year-old girl featuring motor and language delay, whilst child 2 was a 4.5-year-old girl mainly featuring microcephaly and mental retardation. WES revealed that child 2 has harbored a 158.7 kb duplication in Xp11.4 (chrX: 41446160_41604854), which has encompassed exons 4~14 of the CASK gene. The same duplication was not found in either of her parents. aCGH revealed that child 1 has harbored a 29 kb deletion at Xp11.4 (chrX: 41637892_41666665), which encompassed exon 3 of the CASK gene. The same deletion was not found in either of her parents and the fetus. The above results were confirmed by qPCR assay. Above deletion and duplication were not found in the ExAC, 1000 Genomes and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PS2+PM2_Supporting). CONCLUSION The deletion of exon 3 and duplication of exons 4~14 of the CASK gene probably underlay the pathogenesis of MICPCH in these two children, respectively.
Humans ; Child ; Female ; Child, Preschool ; Microcephaly/genetics* ; Developmental Disabilities/genetics* ; Intellectual Disability/complications* ; Comparative Genomic Hybridization ; Mutation

OBJECTIVE: To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. METHODS: Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. RESULTS: The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. CONCLUSION The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.
Pregnancy ; Female ; Humans ; Classical Lissencephalies and Subcortical Band Heterotopias ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Fetus ; Hydrocephalus ; Prenatal Diagnosis ; Chromosome Deletion

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.
Humans ; Child ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Comparative Genomic Hybridization ; Chromosome Disorders/genetics* ; Chromosome Deletion ; Magnetic Resonance Imaging ; Chromosomes, Human, Pair 22 ; Developmental Disabilities/genetics* ; Carrier Proteins/genetics* ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To explore the genetic characteristics of a fetus with a high risk by maternal serum screening during the second trimester. METHODS: Genetic counseling was provided to the pregnant woman on March 22, 2020 at Henan Provincial People's Hospital. G-banded chromosomal karyotyping and array comparative genomic hybridization (aCGH) were carried out on the amniotic fluid sample and peripheral blood samples from the couple. RESULTS: The fetus and the pregnant woman were respectively found to have a 46,XX,der(6)t(6;14)(q27;q31.2) and 46,XX,t(6;14)(q27;q31.2) karyotype, whilst the husband was found to have a normal karyotype. aCGH analysis has identified a 6.64 Mb deletion at 6q26q27 and a 19.98 Mb duplication at 14q31.3q32.33 in the fetus, both of which were predicted to be pathogenic copy number variations. No copy number variation was found in the couple. CONCLUSION The unbalanced chromosome abnormalities in the fetus have probably derived from the balanced translocation carried by the pregnant woman. aCGH can help to determine the types of fetal chromosome abnormalities and site of chromosomal breakage, which may facilitate the prediction of fetal outcome and choice for subsequent pregnancies.
Pregnancy ; Female ; Humans ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Translocation, Genetic ; Chromosome Aberrations ; Fetus ; Prenatal Diagnosis

Objective:To analyze the clinical and genetic characteristics of a 27-year-old male patient with intellectual disability and his pedigree to provide a reference for genetic counseling and prenatal diagnosis.Methods:G-banding and array comparative genomic hybridization (aCGH) were performed to analyze the karyotypes and genomic copy number variations of the proband (Ⅲ-1) and his family members. Based on the results, prenatal diagnosis was performed for one pregnant woman (Ⅲ-2) in the pedigree who is the sister of the proband.Results:All karyotyping were normal in the family members, while aCGH results showed a 1 533 kb microduplication in the Xq25 region of the proband, his mother (Ⅱ-3), his uncle (Ⅱ-2), and his sister (Ⅲ-2), which was confirmed to be pathogenic. The proband and his uncle presented with intellectual disability, bradylalia, and facial dysmorphism. In contrast, his mother and sister showed normal phenotypes. His sister's fetal karyotype and aCGH results were normal, and the pregnancy continued. A male baby (Ⅳ-1) was delivered vaginally at term and showed no physical or intellectual abnormalities during a 46-month follow-up.Conclusions:Xq25 microduplication might be the cause of intellectual disability in the proband. STAG2 is probably the essential gene in Xq25 region.

Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.

Objective:To investigate the prenatal diagnosis and genetic analysis of 9p24 microdeletion in six fetuses.Methods:Genetic data of six pregnant women with positive results of serological Down's syndrome screening at Henan Provincial People's Hospital from January 2018 to January 2020 were retrospectively collected and analyzed. Amniotic fluid and the parents' peripheral blood samples were subjected to G banding and array comparative genomic hybridization (aCGH) analysis. Detected copy number variation (CNV) were classified based on the American College of Medical Genetics and Genomics (ACMG) scoring standard.Results:Six fetuses showed no abnormalities in ultrasound during the second trimester as well as in karyotyping. A chromosome deletion of 1 019~6 001 kb at 9p24 was found in all six fetuses by aCGH, referring to disease-related genes DMRT1, SMARCA2, DOCK8, etc. The deletion of case 3 was inherited from the asymptomatic father, and the other fetal five were all de novo mutations. Cases 1, 2, 5, and 6 were pathogenic/likely pathogenic CNV carriers and cases 3 and 4 were CNV of unknown clinical significance carriers. After genetic counseling, cases 1, 2, 5, and 6 chose to terminate the pregnancies; cases 3 and 4 continued and gave birth to normal offspring. Conclusions:Fetuses with 9p24 microdeletion lack specific phenotypes before born. DMRT1 and SMARCA2 may be the key genes in this region.

Objective:To investigate the association between prenatal genotype and phenotype of 16p13.11 microdeletion syndrome, aiming to provide a reference for prenatal diagnosis and genetic counseling.Methods:This retrospective study analyzed the results of comparative genomic hybridization microarray and low-coverage whole genome sequencing performed on 4 230 pregnant women in the Henan Provincial People's Hospital from July 2018 to July 2021. Indications for prenatal diagnosis, pedigree information and pregnancy outcomes of 17 fetuses with 16p13.11 microdeletion were described.Results:Prenatal diagnostic indications in the 17 fetuses were ultrasound abnormalities in five cases (increased nuchal translucency in four and cerebral ventriculomegaly with 10.7 mm in one), inter-twin weight discordance over 20% in one case, high risk in five cases and marginal risk in one in trisomy-21 serum screening, advanced maternal age in three cases (one with echogenic intracardiac focus in the left ventricle and two with normal ultrasound images) and adverse pregnancy history in two cases with normal ultrasound images. Pedigree verification that performed on 12 cases revealed that five were caused by de novo mutations and seven were inherited from their parents. The follow-up results showed that five cases were terminated, two lost to follow-up and 10 born alive (inheritance patterns were de novo mutations in three cases, parental inheritance in six and unknown pattern in one). These 10 infants were followed up from age 7 months to 3 years and 2 months and the results showed that one case was born with choroid plexus cyst of the left ventricle and presented instability of gait at 1 year and 3 months; one was a premature infant with 33 gestational weeks whose parents reported his language ability was not well at 2 years and 1 month old but without other abnormalities; one case had low muscle tone and was unable to keep head upright at 3 months who recovered at 5 months old after rehabilitation treatment according to the parents' report; all seven parents in the remaining seven cases reported no abnormalities. Conclusions:There was no specific prenatal diagnostic indication for 16p13.11 microdeletion syndrome. Genetic tracing, pregnancy outcome analysis and follow-up surveillance would provide reference for genetic counseling of 16p13.11 microdeletion syndrome.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with mental retardation. METHODS: G-banded karyotyping analysis and single nucleotide polymorphism microarray (SNP array) were used to detect the genetic variants within the family, and the origin of the variants was analyzed using UPDtool Statistics software. RESULTS: The patient, a 26-year-old female, was found to have a chromosomal karyotype of 46,XX,dup(4)(q28.2q31.3),and SNP array revealed a 25.71 Mb duplication at 4q28.2-q31.3. The duplication was inherited from her father, and her fetus was found to carry the same duplication. CONCLUSION The duplication of the patient probably underlay the mental retardation. The gender of the carrier and parental origin of the duplication might have led to the variation in their clinical phenotype.
Adult ; Chromosome Banding ; Female ; Genetic Testing ; Humans ; Karyotyping ; Male ; Pedigree ; Trisomy/genetics*