OBJECTIVE: To explore the clinical features and genetic variants in two children with neonatal severe hyperparathyroidism (NSHPT). METHODS: Two children who were diagnosed with NSHPT at the Children's Hospital Affiliated to Xi'an Jiaotong University respectively in August 2019 and April 2022 were selected as the study subjects. Clinical data were collected, and both children were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. RESULTS: The main clinical features of the two children have included growth delay, hypotonia, hypercalcemia, hypophosphatemia, hyperparathyroid hormonemia, and renal calcium deposition. WES results showed that child 1 has harbored a homozygous c.1378_1G>A splicing variant of the CASR gene, which was unreported previously, whilst child 2 has harbored a homozygous c.2038C>T missense variant of the CASR gene, which was known to be likely pathogenic. Sanger sequencing confirmed that the parents of both children were heterozygous carriers. CONCLUSION The homozygous c.1378_1G>A and c.2038C>T variants of the CASR gene probably underlay the NSHPT in the two children. Discovery of the c.1378_1G>A variant has enriched the mutational spectrum of the CASR gene.
Humans ; Child ; Mutation ; Homozygote

PURPOSE: The beta-adrenoceptors are pharmacologically classified into beta1-, beta2- and beta3-adrenoceptor. The gene of each subtype has polymorphisms related to their function (beta1-adrenoceptor: Ser49Gly, beta2- adrenoceptor: Gln27Glu, beta3-adrenoceptor: Trp64Arg). The objectives of this study were to analyse the allelic and genotypic distribution of the representative polymorphism of beta-adrenoceptors in preeclampsia and to investigate whether combined genotype of beta-adrenoceptors may be associated with preeclampsia. METHODS: Blood samples were collected from a Korean population (159 preeclamptic pregnancies and 168 normotensive pregnancies). The beta1-, beta2- and beta3-adrenoceptor genotypes was determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences in allelic and genotypic distribution of beta1- and beta2-adrenoceptor polymorphisms between the two groups. However, the Arg allele of beta3-adrenoceptor polymorphism were more frequent in preecalmpsia than in controls (P<0.05, OR=1.57, 95% CI=1.01-2.46). Moreover, prevalence of genotype carrying heterozygote of beta3-adrenoceptor polymorphism was increased in preeclampsia compared with controls (P<0.05, OR 1.76, 95% CI 1.06-2.92). When combination of the three polymorphisms were evaluated, pregnancies with the particular combined genotype that is consisted of heterozygote of beta1-, beta3-adrenoceptor and wild homozygote of beta2-adrenoceptor (Ser/Gly, Gln/Gln, Trp/Arg), showed a significant increase in the risk of preeclampsia (P<0.05, OR=3.01, 95% CI 1.12-8.08). CONCLUSION: A particular combined genotype (Ser/Gly, Gln/Gln, Trp/Arg) of - adrenoceptors was associated with the risk of preeclampsia.
Alleles ; Genotype ; Heterozygote ; Homozygote ; Pre-Eclampsia* ; Pregnancy ; Prevalence ; Receptors, Adrenergic

OBJECTIVE: To assess the association of c.109G>A (p.V37I) variant of the GJB2 gene and its types with the risk of deafness. METHODS: PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database were searched for cases with GJB2 gene c.109G>A (p.V37I) variant and its compounds with variants of other sites from case-control studies, cohort studies and cross-sectional studies. The search time was from the establishment of database to April 2021. Two researchers have independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and evaluated the included studies according to the criteria. Stata 12.0 software was used for the meta-analysis and publication bias analysis, and a sensitivity analysis was also carried out when necessary. RESULTS: A total of 22 articles (17 in English and 5 in Chinese) were included. There were 7455 cases in the deafness group and 10 464 cases in the control group. The results of meta-analysis showed the c.109G>A (p.V37I) variant to be strongly associated with the risk of deafness (OR: 3.56, 95%CI: 2.31-5.47, P < 0.001). Analysis based on the mutational type also suggested c.109G>A (p.V37I) homozygosity (OR: 11.36, 95%CI: 5.93-21.74, P < 0.001) and compound loss of heterozygosity mutations (OR: 9.27, 95%CI: 3.97-21.64, P < 0.001) to be strongly associated with the risk of deafness. By contrast, heterozygous c.109G>A (p.V37I) variant (OR: 1.20, 95%CI: 0.72-2.00, P = 0.478) and compound heterozygous missense mutation (OR: 1.54, 95%CI: 0.98-2.44, P = 0.063) are not strongly associated with the risk. CONCLUSION The homozygous c.109G>A (p.V37I) variants of the GJB2 gene and its compound deletional mutation with another GJB2 allele can significantly increase the risk of deafness. Heterozygous c.109G>A (p.V37I) variant of the GJB2 gene or its compound with a missense mutation of another GJB2 allele do not increase the risk.
Humans ; Cross-Sectional Studies ; Alleles ; Heterozygote ; Homozygote ; Deafness/genetics*

with DAT-9 gene allele. And The total score of CIWA-Ar scale in the subject without DAT-9 gene allele was significantly higher than in the subject with DAT-9 gene allele. COMT: The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. CONCLUSION: Our results suggest the relationship between specific genetic factors and the withdrawal symptoms of alcohol dependent patients. As the candidate gene of the severity of alcohol withdrawal syndrome, DRD2 Taq1 gene was recommended.
Alcoholism* ; Alleles ; Heterozygote ; Homozygote ; Humans ; Polymorphism, Genetic ; Substance Withdrawal Syndrome*

The overall prevalence of uniparental disomy (UPD) across all chromosomes was estimated to be around one birth in 2000. To date, more than 4170 UPD cases have been registered. UPD for chromosomes 6, 7, 11, 14, 15, and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression. For other chromosomes, the clinical consequences associated with UPD are not apparent, unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity (ROH). A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD. This guideline summarizes the conception, mechanism and clinical consequences of ROH/UPD, as well as the principles for data analysis, with an aim to standardize the clinical application and data interpretation.
Gene Expression ; Genomic Imprinting ; Homozygote ; Humans ; Uniparental Disomy/genetics*

Male ; Humans ; Azoospermia/genetics* ; Infertility, Male/genetics* ; Mutation ; Homozygote

BACKGROUND: In Korean population, antigen frequencies of HNA-1a, HNA-1b, and HNA-2a are determined using a serological and genotyping method. However, no study has been done to assess the gene frequencies of HNA-4a and HNA-5a. It has been reported that the antibody against HNA-4a is associated with alloimmune neutropenia and autoimune neutropenia; however, there is no confirmed clinical report on anti-HNA-5a-related disorders. The aim of this study was to determine HNA-4a and HNA-5a gene frequencies among the Korean population. METHODS: Genotyping of HNA-4a and HNA-5a genes of 110 healthy and unrelated Korean donors was performed using a polymerase chain reaction with sequence-specific primers and an allelespecific restriction enzyme analysis. RESULTS: We found that the gene frequencies of HNA-4a and HNA-5a were 0.99 (107/110) and 0.96 (3/110), respectively, among the Korean population. But only the ones of the latter was significantly higher (P<0.01) than in the one of Caucasians. CONCLUSIONS: The gene frequencies of HNA-4a and HNA-5a were determined. We also identified an individual who was the HNA-5a-negative homozygote for the granulocyte panel that could be used for anti-HNA-5a antibody identification.
Gene Frequency* ; Granulocytes ; Homozygote ; Humans* ; Neutropenia ; Neutrophils* ; Polymerase Chain Reaction ; Restriction Mapping ; Tissue Donors

OBJECTIVE: To explore the association of p53 codon 72 polymorphism with endometriosis. METHODS: Two hundred seventy-one women with surgically or histologically diagnosed edometriosis of stage I-IV, and 219 patients with no evidence of endometriosis by laparoscopy or laparotomy served as control. Allele frequencies and genotype distribution of p53 polymorphisms (arginine homozygosity, heterozygosity, and proline homozygosity) in affected women and controls were evaluated. RESULTS: The genotype distributions of p53 codon 72 polymorphisms did not differ significantly between endometriosis group and control group (p=0.086). However, the genotype distributions of p53 codon 72 polymorphisms differ significantly between stage I-II endometriosis group and control group (p=0.043). Proline homozygotes had higher risk for stage I-II endometriosis compared to arginine homozygotes (odds ratio=2.75, p=0.013). CONCLUSION: These results suggest that proline homozygote of p53 codon 72 polymorphism is associated with the risk of minimal or mild stage of endometriosis in the Korean population.
Arginine ; Codon* ; Endometriosis* ; Female ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Laparoscopy ; Laparotomy ; Proline

BACKGROUND: Alloantibodies against human neutrophil alloantigen (HNA)-3a are associated with severe and fatal transfusion related acute lung injury (TRALI). HNA-3 genotyping and HNA-3a antibody (Ab) identification are essential to diagnosis and prevention of TRALI caused by HNA-3a Ab. However there had been no laboratory for HNA-3a Ab identification in Korea. The aims of this study were to establish the HNA-3a Ab test in Korea and to estimate the incidence of HNA-3a alloimmunization among pregnant Korean women. METHODS: HNA-3a homozygotes and HNA-3b homozygotes were identified by HNA-3 genotyping. Three HNA-3a homozygotes and three HNA-3b homozygotes are included in the granulocytes panel, which consisted of 10 donors for granulocytes. Sera from 650 pregnant Korean women were tested for granulocyte Ab using a mixed passive hemagglutination assay (MPHA). When a HNA-3a Ab was detected, the woman's HNA-3 was typed to support her HNA-3a alloimmunization. RESULTS: MPHA showed positive reactions in the sera from 26 women (4.0%, 26/650). HLA Abs were detected in 18 women (2.8%, 18/650), among whom HNA Abs were identified simultaneously in 7 women. Granulocyte Abs were detected in sera from 15 women (2.3%, 15/650). The incidence of HNA-3a, HNA-1b, HNA-1a, HNA-2a, and unidentified HNA Abs among pregnant Korean women was 0.77% (5/650), 0.77% (5/650), 0.62% (4/650), 0.15 (1/650), and 0.31% (2/650), respectively. CONCLUSION: In this study, we established the HNA-3a Ab test using MPHA for diagnosis and prevention of TRALI caused by HNA-3a Ab. The incidence of HNA-3a Ab in pregnant Korean women was 0.77% (5/650).
Acute Lung Injury ; Diagnosis ; Female ; Granulocytes ; Hemagglutination ; Homozygote ; Humans* ; Incidence ; Isoantibodies ; Isoantigens ; Korea ; Neutrophils* ; Tissue Donors

OBJECTIVE: To estimate the association between ABCG2 C421A polymorphism and response to imatinib in chronic myeloid leukemia. METHODS: A systematic review was conducted to evaluate the effect of ABCG2 C421A polymorphism on imatinib response. The databases of PubMed, Embase, Web of science, CINAHL with FullText, and Cochrane Library were searched for all published studies from inception to December 2015. The following terms were used with functions of 'AND' and 'OR': 'chronic myeloid leukemia', 'CML', 'drug transporter', 'ABCG2', 'BCRP', 'polymorphisms', 'SNPs', and 'imatinib'. The studies reporting the association between ABCG2 polymorphism and imatinib response were evaluated. RESULTS: A total of 7 studies were included in the present meta-analysis. The pooled analysis showed that ABCG2 c.421CC genotype was significantly associated with poor response to imatinib under the dominant model (CC vs CA+AA; OR: 0.56; 95% CI: 0.41, 0.77; p = 0.0004). The subgroup analysis of Asian studies demonstrated a significantly lower response in c.421CC genotype than in c.421CA or c.421AA genotype (OR: 0.52; 95% CI: 0.37, 0.73; p = 0.0002). In subgroup analyses of 5 studies, the patients with the c.421CC genotype exhibited higher risk for worse response than the patients with c.421CA or c.421AA genotype (heterozygote codominant model: CC vs. AC; OR: 0.49, 95% CI: 0.33, 0.73; p = 0.0006; homozygote codominant model: CC vs AA; OR: 0.43; 95% CI: 0.25, 0.75, p = 0.003). CONCLUSION: The ABCG2 c.421CC genotype was significantly associated with poor response to imatinib compared to the c.421CA and c.421AA genotypes in chronic myeloid leukemia, especially in Asian patients.
Asian Continental Ancestry Group ; Genotype ; Homozygote ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Imatinib Mesylate