OBJECTIVE: To explore the genetic characteristics of a child with Focal segmental glomerulosclerosis and neurodevelopmental syndrome (FSGSNEDS). METHODS: A child with FSGSNEDS who had visited Shengli Oilfield Central Hospital on September 15, 2019 was selected as the study subject. Clinical data of the child was collected, and trio-whole exome sequencing (trio-WES), Sanger sequencing, chromosomal karyotyping analysis, and copy number variation sequencing (CNV-seq) were used to analyze the child and his parents. RESULTS: The child, a 3-year-old boy, had manifested developmental delay, nephrotic syndrome, and epilepsy. Trio-WES and Sanger sequencing showed that he has carried a heterozygous c.1375C＞T (p.Q459*) variant of the TRIM8 gene, for which both his parents were of the wild type. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. No abnormality was found in the chromosomal karyotyping and CNV-seq results of the child and his parents. CONCLUSION The child was diagnosed with FSGSNEDS, for which the c.1375C＞T variant of the TRIM8 gene may be accountable.
Male ; Humans ; Child ; Child, Preschool ; DNA Copy Number Variations ; Glomerulosclerosis, Focal Segmental/genetics* ; Genomics ; Heterozygote ; Karyotyping ; Carrier Proteins ; Nerve Tissue Proteins

OBJECTIVE: To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS). METHODS: An infant suspected for SYS at the Hunan Provincial Children's Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and mutant proteins was constructed to analyze the potential hazard. RESULTS: The infant was found to harbor a heterozygous frameshifting variant of c.1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function. CONCLUSION The c.1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.
Humans ; Infant ; Down-Regulation ; Heterozygote ; Mutation ; Parents ; Proteins

OBJECTIVE: To explore the clinical features and genetic variant in a child with Cerebral creatine deficiency syndrome (CCDS). METHODS: A child who had presented at the Affiliated Children's Hospital of Fudan University on March 5, 2021 was selected as the study subject. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing. The level of creatine in the brain was determined by magnetic resonance spectroscopy. RESULTS: The patient, a 1-year-and-10-month male, had presented with developmental delay and epilepsy. Both his mother and grandmother had a history of convulsions. MRS showed reduced cerebral creatine in bilateral basal ganglia and thalamus. The child was found to harbor a hemizygous splicing variant of the SLC6A8 gene, namely c.1767+1_1767+2insA, which may lead to protein truncation. The variant was not found in the public databases. Both his mother and grandmother were heterozygous carriers for the same variant. CONCLUSION The hemizygous c.1767+1_1767+2insA variant of the SLC6A8 gene probably underlay the CCDS in this child. Discovery of the novel variant has also expanded the mutational spectrum of the SLC6A8 gene.
Humans ; Male ; Amino Acid Metabolism, Inborn Errors ; Brain ; Creatine/genetics* ; Heterozygote ; Mothers ; Nerve Tissue Proteins ; Plasma Membrane Neurotransmitter Transport Proteins/genetics* ; Infant

OBJECTIVE: To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure. RESULTS: The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant. CONCLUSION The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.
Humans ; Male ; Female ; Pedigree ; Factor XII/genetics* ; Mutation ; East Asian People ; Heterozygote ; Mothers ; Factor XII Deficiency/genetics*

OBJECTIVE: To analyze the prevalence, genotype distribution and hematological characteristics of α,β-thalassaemia carriers in Huizhou area of Guangdong Province. METHODS: 10 809 carriers of simple β-thalassaemia and 1 757 carriers of α,β-thalassaemia were enrolled as our study cohort. The hematological parameters were detected by automated blood cell counters and automatic capillary electrophoresis. Suspension array technology, gap-polymerase chain reaction (gap-PCR) and PCR-reverse dot blot were used for the genotyping of thalassaemia carriers. RESULTS: The prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province was 1.99%. A total of 62 genotypes were detected, and the most prevalent genotype was --^SEA/ αα, β^CD41-42/ β^N (19.29%), the next was --^SEA/ αα, β^IVS-II-654/ β^N (16.73%). Significant differences in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were found between different genotype groups for simple β-thalassaemia and α,β-thalassaemia. Violin plots showed that carriers with co-inheritance of β-thalassaemia and mild α-thalassaemia expressed the lightest anemia, and carriers with co-inheritance of β-thalassaemia and hemoglobin H (Hb H) disease expressed the most severe anemia. CONCLUSION There is a high prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province. Because of the lack of specific hematological makers for diagnosis of α,β-thalassaemia, it is necessary to distinguish it from simple β-thalassaemia by genotyping of α- and β-thalassaemia in order to correctly guide genetic counseling and prenatal disgnosis.
Pregnancy ; Female ; Humans ; beta-Thalassemia/genetics* ; Genotype ; Heterozygote ; Phenotype ; alpha-Thalassemia/genetics* ; China/epidemiology* ; Mutation

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Humans ; Intellectual Disability/genetics* ; Genetic Testing ; Phenotype ; Exome Sequencing ; Heterozygote ; Mutation ; Chromosomal Proteins, Non-Histone/genetics* ; Phosphoproteins/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Schaaf-Yang syndrome (SYS). METHODS: Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Sanger sequencing was used for family constellation verification, and bioinformatic analysis was performed for the candidate variant. RESULTS: The child, a 1-year-and-9-month-old boy, had clinical manifestations of retarded growth, small penis, and unusual facies. Genetic testing revealed that the child has harbored a novel heterozygous variant of c.3078dupG (p.Leu1027Valfs*28) of the MAGEL2 gene. Sanger sequencing showed that neither parent of the child carried the same variant. The c.3078dupG(p.Leu1027Valfs*28) variant of the MAGEL2 gene has not been included in the databases of ESP, 1000 Genomes and ExAC. According to the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was judged to be pathogenic. CONCLUSION The c.3078dupG (p.Leu1027Valfs*28) variant of the MAGEL2 gene probably underlay the SYS in this child, which has further expanded the spectrum of the MAGEL2 gene variants.
Child ; Humans ; Infant ; Male ; Exome Sequencing ; Genetic Testing ; Heterozygote ; Mutation ; Proteins/genetics* ; Developmental Disabilities/genetics*

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing. RESULTS: The child was found to harbor a c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent. CONCLUSION The c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants and provided a basis for the diagnosis and treatment for this child.
Child ; Humans ; Intellectual Disability/genetics* ; Frameshift Mutation ; High-Throughput Nucleotide Sequencing ; Computational Biology ; Heterozygote ; Mutation ; ras GTPase-Activating Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a child with Aspartylglucosaminuria (AGU). METHODS: Clinical data of the patient was analyzed. The child was subjected to trio-whole exome sequencing (WES) and copy number variation sequencing (CNV-seq), and candidate variant was verified by Sanger sequencing. RESULTS: The child was found to harbor homozygous c.319C>T (p.Arg107*) nonsense variant of the AGA gene, for which both of his parents were heterozygous carriers. No abnormality was found by CNV-seq analysis. The c.319C>T (p.Arg107*) variant was not found in population database, HGMD and other databases. Based on guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP3). CONCLUSION The c.319C>T variant of the AGA gene probably underlay the autosomal recessive AGU in this child. Above finding has enabled genetic counseling and prenatal diagnosis for his parents.
Female ; Pregnancy ; Humans ; Child ; Aspartylglucosaminuria ; DNA Copy Number Variations ; Genetic Counseling ; Genomics ; Heterozygote ; Mutation

OBJECTIVE: To explore the clinical phenotype and genetic basis for a Chinese pedigree affected with Oral-facial-digital syndrome type I (OFD1). METHODS: A pedigree with OFD1 who presented at Hebei General Hospital on March 17, 2021 was selected as the subject. Clinical data of the child was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband and members of her pedigree, and candidate variant was verified by Sanger sequencing. RESULTS: The proband has featured hypotelorism, broad nasal root, flat nasal tip, lobulated tongue, tongue neoplasia, camptodactyly of left fifth finger, syndactyly of right fourth and fifth fingers, and delayed intellectual and language development. Trio-WES revealed that the proband and her daughter, sister and mother have harbored a heterozygous c.224A>G (p.Asn75Ser) variant of the OFD1 gene. The same variant was not found among healthy members from her pedigree. CONCLUSION The c.224A>G (p.Asn75Ser) variant probably underlay the OFD1 in this pedigree. Above discovery has enriched the spectrum of OFD1 gene variants.
Humans ; Female ; Pedigree ; Orofaciodigital Syndromes/genetics* ; East Asian People ; Phenotype ; Heterozygote ; Mutation ; China