OBJECTIVES: To study the characteristics of UGT1A1 gene mutations in Dong neonates in Sanjiang County of Liuzhou and its association with the pathogenesis of hyperbilirubinemia in Dong neonates. METHODS: A prospective analysis was performed on 84 neonates who were diagnosed with unexplained hyperbilirubinemia in the Department of Neonatology, Sanjiang County People's Hospital, from January 2021 to January 2022. Sixty healthy neonates born during the same period were enrolled as the control group. Peripheral blood genomic DNA was extracted for both groups, and UGT1A1 exon 1 was amplified by PCR and sequenced. RESULTS: In the case group, 33 neonates were found to have G71R missense mutation, with a mutation rate of 39%. The case group had a significantly higher frequency of A allele than the healthy control group (21% vs 10%, P<0.05). The risk of hyperbilirubinemia in Dong neonates carrying G71R missense mutation was 2.588 times as high as that in healthy neonates carrying wild-type UGT1A1 gene (P<0.05). Hardy-Weinberg equilibrium testing showed that the UGT1A1 G71R locus was in genetic equilibrium in both groups (P>0.05). CONCLUSIONS UGT1A1 G71R mutation is a high-frequency gene mutation type in Dong neonates in Sanjiang County, and G71R missense mutation is associated with hyperbilirubinemia in Dong neonates.
Asians/genetics* ; China ; Exons ; Glucuronosyltransferase/genetics* ; Humans ; Hyperbilirubinemia, Neonatal/genetics* ; Infant, Newborn ; Mutation

OBJECTIVE: To explore the association of single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene ( VDR) with circulating lipids considering gender differences. METHODS: Of the Han Chinese adults recruited from a health examination center for inclusion in the study, the circulating lipids, 25-hydroxyvitamin D (25OHD), and other parameters were measured. The VDR SNPs of Cdx2 (rs11568820), Fok1 (rs2228570), Apa1 (rs7975232), and Taq1 (rs731236) were genotyped with a qPCR test using blood DNA samples, and their associations with lipids were analyzed using logistic regression. RESULTS: In the female participants ( n = 236 with dyslipidemia and 888 without dyslipidemia), multiple genotype models of Fok1 indicated a positive correlation of B (not A) alleles with LDLC level ( P < 0.05). In the male participants ( n = 299 with dyslipidemia and 564 without dyslipidemia), the recessive model of Cdx2 and the additive and recessive models of Fok1 differed ( P < 0.05) between the HDLC-classified subgroups, respectively, and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC ( P < 0.05). CONCLUSION In the Chinese Han adults included in the study, the Fok1 B-allele of VDR was associated with higher LDLC in females, and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males. The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.
Adult ; Alleles ; Asians/genetics* ; China/ethnology* ; Dyslipidemias/genetics* ; Female ; Genetic Predisposition to Disease/genetics* ; Genotype ; Humans ; Lipids/blood* ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol/genetics* ; Sex Factors ; Vitamin D/blood*

OBJECTIVE: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. METHODS: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. RESULTS: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. CONCLUSION Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.
Asians ; Case-Control Studies ; Cleft Lip/genetics* ; Cleft Palate/genetics* ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Mutation ; Parents ; Polymorphism, Single Nucleotide ; Whole Exome Sequencing

OBJECTIVE: To explore the genotype mutation characteristics of patients with glucose-6-phosphate dehydrogenase(G6PD) deficiency in Wuhan. METHODS: A total of 1 321 neonates with positive screening and outpatients were received G6PD mutation detection, 12 kinds of common G6PD mutation in Chinese people was detected by using multicolor melting curve analysis (MMCA) method, for those with negative results, the enzyme activity and clinical information were analyzed, sequencing was recommended after informed consent when it is necessary. RESULTS: Among 1321 patients, a total of 768 mutations were detected out, with a detection rate of 58.1%. A total of 18 types of G6PD genotypes were identified, including c.1388G>A, c.1376G>T, c.95G>A, c.1024C>T, c.871G>A, c.392G>T, c.487G>A, c.1360C>T, c.1004C>A, c.517T>C, c.592C>T, c.94C>G, c.152C>T, c.320A>G, c.1028A>G, c.1316G>A, c.1327G>C and c.1376G>C, including 683 male hemizygotes, 3 female homozygotes, 80 female heterozygotes and 2 female compound heterozygous. CONCLUSION A total of 18 types of G6PD mutations are identified in the reaserch, and c.94C>G, c.1028A>G and c.1327G>C are first reported in Chinese population. The most common G6PD mutation types in Wuhan are c.1388G>A, c.1376G>T, c.95G>A.
Asians/genetics* ; Female ; Genotype ; Glucosephosphate Dehydrogenase/genetics* ; Glucosephosphate Dehydrogenase Deficiency/genetics* ; Heterozygote ; Humans ; Infant, Newborn ; Male ; Mutation

OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a Chinese patient with retinitis pigmentosa (RP). METHODS: Whole exome sequencing (WES) was carried out to screen potential variant in the proband. Candidate variants were determined by taking consideration of clinical phenotype. Sanger sequencing was used to verify the variant in the proband and his parents. RESULTS: The proband was found to harbor compound heterozygous variants of c.8G>A (p.Cys3Tyr) and c.958_959insA (p.Arg320Glnfs*29) in the C2ORF71 gene, which has derived from his father and mother, respectively. Both variants were unreported previously. Based on the ACMG guidelines, they were predicted to be likely pathogenic and pathogenic, respectively. CONCLUSION The novel compound heterozygous variants of the C2ORF71 gene probably underlay the pathogenesis of RP in the proband. Above finding has enriched the spectrum of C2ORF71 gene mutations and facilitated genetic counseling for the family.
Asians/genetics* ; China ; Humans ; Mutation ; Pedigree ; Retinitis Pigmentosa/genetics* ; Whole Exome Sequencing

OBJECTIVE: To analyze the clinical features and variants of ABCD1 gene in a Chinese pedigree affected with X-linked adrenoleukodystrophy. METHODS: Clinical data of the proband were collected and analyzed. Potential variant of the ABCD1 gene were analyzed by PCR and Sanger sequencing of the proband, his parents and 100 unrelated healthy individuals. RESULTS: The prominent features of the proband included cerebellar and brainstem lesions, along with increased serum level of very-long chain fatty acids. He was found to harbor a hemizygous c.1509delG (p.L504Sfs*54) variant of the ABCD1 gene, for which his mother was heterozygous. The same variant was not detected in his father and 100 healthy controls. CONCLUSION X-linked adrenoleukodystrophy has a variety of clinical manifestations. Discovery of the c.1509delG (p.L504Sfs*54), as a novel pathogenic variant of the ABCD1 gene, has enabled diagnosis and genetic counseling for this pedigree.
Adrenoleukodystrophy/genetics* ; Asians/genetics* ; China ; Female ; Genetic Testing ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVE: To analyze the clinical phenotype and genetic variant in a Chinese pedigree affected with benign familial neonatal convulsion (BFNC). METHODS: Clinical data and peripheral blood samples of the pedigree were obtained with informed consent. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing. RESULTS: The pedigree comprised 9 individuals, among whom 4 were affected, including 3 males and 1 female. All patients had developed seizures during the neonatal period, which had ceased in 4 to 6 months. One patient had recurrence in between 1 and 2 years old. Genetic testing has identified a novel nonsense c.810G>A (p.W270X) variant in exon 5 of the KCNQ2 gene, which has co-separated with the BFNC phenotype in the pedigree. CONCLUSION The patients from this pedigree have conformed to the diagnosis of BFNC with good prognosis, which was in keeping with previously reported cases. The heterozygous c.810G>A (p.W270X) nonsense variant of the KCNQ2 gene probably underlay the pathogenesis of BFNC in this pedigree, which has expanded the mutational spectrum of the disease.
Asians/genetics* ; Child, Preschool ; China ; Epilepsy, Benign Neonatal/genetics* ; Female ; Genetic Testing ; Humans ; Infant ; Male ; Mutation ; Pedigree

OBJECTIVE: To study the polymorphism of human platelet antigen (HPA) system 10 among ethnic Han Chinese from Shandong, China so as to supplement the data of platelet donor bank in the region. METHODS: Peripheral blood samples of platelet donors from the region were genotyped for HPA-10 alleles by PCR-sequence specific primer (PCR-SSP) and direct sequencing. RESULTS: Among 1401 donors, a rare heterozygote carrier of HPA-10w (a+b+) was identified, which gave an allelic frequency of approximately 0.035%. CONCLUSION The detection of rare HPA-10bw antigen allele among ethnic Han Chinese from Shandong is useful for the diagnosis and prevention of neonatal alloimmune thrombocytopenia and post-transfusion purpura in the region.
Alleles ; Antigens, Human Platelet/genetics* ; Asians/genetics* ; Gene Frequency ; Genotype ; Humans ; Infant, Newborn ; Polymorphism, Genetic

OBJECTIVE: To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age. METHODS: A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed. RESULTS: One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria. CONCLUSION This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.
Asians/genetics* ; China ; Exome ; Female ; Humans ; Infant, Newborn ; Metabolic Diseases/genetics* ; Mitochondrial Membrane Transport Proteins/genetics* ; Oxidoreductases/genetics* ; Whole Exome Sequencing