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

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*

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*

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

Except for the hallux, the human toes classically present three phalanges, distal, middle and proximal. However in 5th toe, only two phalanges are frequently observed. In this condition, known as synarthrosis of the distal interphalangeal joint, the middle and distal phalanges are fused together to appear as symphalangism or biphalangeal 5th toe. Phalanges of 5th toe was investigated in 1,187 cases of Korean radiographs. The incidence of symphalangism was found to be 74% in 1,150 adult. The bilaterality was 99%. To prove proove the genetic basis of the symphalangism, pedigree studies were performed. The symphalangism of the 5th toe was supposed to be an autosomal dominant trait. As an phenotype of recessive homozygote the triphalaneal subjects were traced to investigate their families. Pedigrees of four families in which both parents had triphalangea of 5th toe showed that their offsprings always showed the triphalangea. Therefore, it suggests the symphalangism inherit as a Mendelian dominant trait and it seems to be an example of microevolution or genetic adaptation to bipedalism.
Adult ; Genetics ; Hallux ; Homozygote ; Humans ; Incidence ; Joints ; Parents ; Pedigree ; Phenotype ; Toes*

The C57BL/6J-fe/fe mouse is a coat color mutant. The coat color of the homozygote mouse becomes progressively lighter with advancing age. The faded gene (fe) of C57BL/6J-fe/fe was mapped in a 2.0 cM distal to D10mit191 by our group. To make a high-resolution map, we used the Korean wild mouse (KWHM) for a backcross panel, which was captured in 1995 and has been maintained as an inbred line by our laboratory. In the inter-specific backcross panel (N=400), the fe gene was mapped to 1.0 cM distal to D10mit156. The gene order was defined: centromere -D10mit3/85 (1.3+/-0.6 cM)-D10mit155 (1.3+/-0.6 cM)-D10mit191 (2.0+/-0.7 cM)-D10mit156 (1.0+/-0.5 cM)-fe-D10mit193 (1.3+/-0.6 cM)-D10mit54 (1.0+/-0.5 cM)-D10mit44 (8.5+/-1.4 cM)-D10mit42 (10.0+/-1.5 cM). The measured distance between D10mit191 and D10mit 44 differed in both inter-specific (DBA/2) and intra-specific (KWHM) backcross panels (14.2 vs 13.8 cM). Taken together, our high-resolution linkage map of the fe locus from an intra-specific backcross panel will provide a good entry point to isolate the fe gene.
Animals ; Centromere ; Chromosomes, Human, Pair 10 ; Gene Order ; Hair Color ; Homozygote ; Mice

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

OBJECTIVES: Recently, there has been a growing enthusiasm in biological approach to personality; the identification of genes responsible for particular personality traits. The aim of this study was to investigate the association between the 5-HT1Dbeta G861C polymorphism and personality traits. METHODS: We recruited 218 normal subjects. The Korean version of the Temperament and Character Inventory (TCI) was used to assess personality traits. From blood samples taken from the subjects, DNA was isolated using standard techniques and the HT1Dbeta G861C polymorphism was genotyped by means of polymerase chain reaction and Homogeneous MassEXTEND method. We classified the subject into the GG, CG, and GG groups according to their genotypes. The differences in the temperament factors of the TCI between homozygote group (GG+CC genotype) and heterozygote group (CG genotype) were tested. RESULTS: The heterozygote group had significantly lower Harm avoidance (HA) scores and higher Self-directedness scores (SD) than the homozygote group. CONCLUSION: In conclusion, we found some associations between the 5-HT1Dbeta G861C polymorphism and the personality dimension HA and SD in a normal population.
DNA ; Genotype ; Heterozygote ; Homozygote ; Polymerase Chain Reaction ; Receptor, Serotonin, 5-HT1B* ; Temperament