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*

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

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*

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*

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cerebrovascular disease. MTHFR 677TT genotype can induce hyperhomocysteinemia. However, the association between this 677TT genotype and ischemic stroke still remains controversial. This study was undertaken to determine whether MTHFR 677TT genotype was associated with certain subtype of ischemic stroke. METHODS: The case group consisted of 129 patients with ischemic stroke and the control group consisted of 157 healthy individuals. We checked their fasting plasma homocysteine levels and analyzed the C677T mutation in the MTHFR gene. The relative risk of MTHFR 677TT genotype was assessed by odds ratios using multivariate logistic regression. RESULTS: Homocysteine levels in plasma were significantly higher in ischemic stroke patients (10.386.44 mol/L) than in controls (8.002.40) (P<0.05). In small-artery disease (11.366.01), the same result was found (P<0.05). On the other hand, the prevalence of the homozygote mutation was not significantly higher in ischemic stroke patients (20.2%) than in controls (13.4%) (adjusted OR 1.39, 95% CI 0.65 to 2.96). The adjusted OR and 95% CI was 2.59 (1.08 to 6.25) for the TT genotype in patients with small-artery disease compared to controls. The 677TT genotype was increased in small-artery disease compared to large-artery disease (adjusted OR 7.60, 95% CI 1.66 to 34.77). CONCLUSIONS: Our findings suggest that the homozygous C677T mutation in the MTHFR gene is a risk predictor in the subtype of ischemic stroke, such as small-artery disease.
Fasting ; Genotype ; Hand ; Homocysteine ; Homozygote ; Humans ; Hyperhomocysteinemia* ; Logistic Models ; Odds Ratio ; Plasma ; Prevalence ; Risk Factors ; Stroke*

Idiopathic renal hypouricemia is a disorder characterized by impaired urate handling in the renal tubules. Most patients with hypouricemia are asymptomatic and are found incidentally, but the condition is known to be at high risk for exercise-induced acute renal failure or urolithiasis. URAT1 protein encoded by SLC22A12 gene has been identified recently as a urate/anion exchanger in the human kidney. Inactivation mutations in SLC22A12 gene have been shown to cause renal idiopathic hypouricemia. We experienced a 3-year-old boy who presented with persistent orange-colored urine since infancy. His urine contained many uric acid crystals, while the serum showed hypouricemia(0.7 mg/dL). The fractional excretion of uric acid was increased to 41.7%. SLC22a12 gene analysis revealed W258X homozygote alleles. Renal hypouricemia must be included in the differential diagnosis of red-urine and SLC22A12 gene analysis is recommended in idiopathic renal hypouricemia.
Acute Kidney Injury ; Alleles ; Child, Preschool ; Diagnosis, Differential ; Homozygote ; Humans ; Kidney ; Male ; Uric Acid ; Urolithiasis

PURPOSE: Endometriosis is a steroid dependent disease with a particular genetic background but the location of possible genomic aberrations are still poorly clarified. This study was designed to investigate the associations between the polymorphism of the progesterone receptor gene (PROGINS) and endometriosis. METHODS: 100 women with surgically diagnosed and histologically confirmed endometriosis were enrolled as a patient population and a total of 110 female control subjects undergoing health examination were enrolled as control population. DNA extraction and polymerase chain reaction (PCR) were used to genotype women for the presence of the PROGINS polymorphism in peripheral blood samples. The x2-test was used to compare genotype distributions between endometriosis and controls. RESULTS: T1/T2 heterozygote was found to be one patient in each group, and the rest of the subjects were all T1/T1 homozygotes. There was no difference in the genotype distribution between the endometriosis group and the control group. CONCLUSION: These results suggest that the progesterone receptor gene PROGINS is not associated with the risk for endometriosis.
DNA ; Endometriosis* ; Female ; Genotype ; Heterozygote ; Homozygote ; Humans ; Polymerase Chain Reaction ; Progesterone* ; Receptors, Progesterone*

PURPOSE: Development of asthma involves the interaction between genetic factors and environmental stimuli. This study aims to investigate whether major single nucleotide polymorphism (SNP)s and their haplotypes of the ADRB2 (beta2-adrenoceptor) gene are associated with children with asthma in Korea. METHODS: Children with asthma aging 5 to 15 years old were recruited as the patient group, and children without respiratory diseases or asthma of the same age were recruited as the control group. Blood samples of 5 mL were collected and DNA was extracted by standard methods. Genotyping was done for 6 SNPs known to have a frequency of more than 4%, including 1309A>G, 1342C>G, 1515G>A, 1786C>A, 2316G>C, 2502G>A. RESULTS: Overall, 438 subjects (214 patients and 224 controls) were included in this study. Minor allele homozygote frequency of 6 SNP were 22%, 1.8%, 11%, 12.3%, 21.2% and 13.0%, respectively. Differences between both groups of individual SNP frequencies were not statistically significant, although the difference of the frequency of the second SNP (1342C>G) has borderline significance (P=0.06). Overall distributions of haplotypes were not significantly different between both groups. However, analysis of specific SNPs among haplotypes revealed that haplotypes including the 2nd SNP were significantly associated with asthma (odds ratio, 1.7; 95% confidence interval, 1.1 to 2.6). Combinations of haplotypes excluding the 2nd SNP did not show significant difference between both groups. CONCLUSION: This study suggests that the ADRB2 gene polymorphism is associated with susceptibility to childhood asthma and that analysis of haplotypes rather than SNPs is more reliable in this association.
Aging ; Alleles ; Asthma ; Child ; DNA ; Haplotypes ; Homozygote ; Humans ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic, beta-2