Association of biliverdin reductase A gene polymorphisms with neonatal hyperbilirubinemia from Fujian area / 中华实用儿科临床杂志

Objective To assess the association of single nucleotide polymorphisms (SNPs)of biliverdin reductase A (BLVRA) with neonatal hyperbilirubinemia from Fujian area.Methods A total of 286 patients with neonatal hyperbilirubinemia and 250 healthy controls were enrolled.Genotypes of 5 SNPs within BLVRA gene including rs699512,rs1802846,rs7738,rs1637530 and rs2302032 were determined with matrix-assisted laser desorption ionization/time of flight mass spectrometer.The frequencies of genotype,allele,haplotype and their differentiations were analyzed.Results All 5 SNPs had conformed to Hardy-Weinberg equilibrium (all P ＞ 0.05).rs699512 and rs1637530 showed a significant difference between the 2 groups in both allelic and genotypic frequencies (all P ＜ 0.05),but no significant differences were found in the other SNPs(all P ＞ O.05).In recessive model,the frequency of rs699512 GG genotype of patients was significantly lower than that of the healthy control group(OR =0.494,95％ CI:0.276-0.886,P =0.018),while in dominant model,the frequencies of rs699512 GG + AG and rs1637530 TT + CT genotype of patients were significantly lower than that of the healthy control group(OR =0.678,0.627;95％ CI:0.482-0.954,0.444-0.885;P =0.026,0.008).Based on linkage disequilibrium analysis and haplotype construction,rs1637530,rs2302032,rs699512 and rs1802846 locus in the same area.Based on haplotype CGAT,TGGT,CTAT and CGGT had significant differences between the 2 groups (all P ＜ 0.05),and could reduce the risk of high blood bilirubin (OR =0.588,0.687,0.501;95％ CI:0.434-0.797,0.496-0.952,0.250-1.004).Conclusions rs699512 and rs1637530 may be associated with neonatal hyperbilirubinemia,A allele in rs699512 and C allele in rs1637530 may be associated with significantly increased risk of neonatal hyperbilirubinemia.

Analysis of GCDH gene mutations in 3 patients from Fujian area with glutaric academia type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore clinical features and mutation types in patients from Fujian area with glutaric academia type I(GA I).</p><p><b>METHODS</b>Serum acylcarnitine and urine organic acid of 3 patients were determined with tandem mass spectrometry and gas chromatographic mass spectrometry. The patients also underwent magnetic resonance imaging analysis for the cranial region. Genomic DNA was extracted from peripheral blood samples, and the 12 exons and flanking regions of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing. One hundred healthy newborns were used as controls.</p><p><b>RESULTS</b>Mutations of the GCDH gene were identified in all of the 3 patients. Two patients have carried compound heterozygous mutations including c.1244-2A>C and c.1147C>T(p.R383C), c.406G>T(p.G136C) and c.1169G>A(p.G390E), respectively. One has carried homozygous c.1244-2A>C mutation. The same mutations were not detected among the 100 healthy newborns. Only one patient received early intervention and did not develop the disease. The other two had irreversible damagesto their intelligence.</p><p><b>CONCLUSION</b>c.1169G>A(p.G390E) is likely pathogenic mutations for GA I patients from Fujianarea. Early screening of neonatal metabolic diseases is crucial for such patients.</p>

Analysis of CYP21A2 gene mutations among patients with classical steroid 21-hydroxylase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the frequencies of CYP21A2 gene mutations among patients from Fujian area with classical 21-hydroxylase deficiency.</p><p><b>METHODS</b>For 19 probands from different families affected with classical steroid 21-hydroxylase deficiency and 74 family members, mutations of the CYP21A2 gene were analyzed with combined nested polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification. Time resolved fluorescence immunoassay was performed to determine the level of 17-hydroxyprogesterone (17-OHP) in all family members. Clinical data and laboratory results of the probands and their family members were analyzed.</p><p><b>RESULTS</b>Eleven mutations were identified among the 38 alleles from the 19 probands. 92.1% (35/38) of the mutant CYP21A2 alleles were due to recombination between CYP21A2 and CYP21A1P. Gene conversion and deletions were identified in 84.2% (32/38) and 7.9% (3/38) of the alleles, respectively. IVS2-13A/C>G and chimeras were the most common mutations, which respectively accounted for 34.2% (13/38) and 18.4% (7/38) of all mutant alleles. Among these, IVS2+1G>A and Q318X+356W were first reported in China. 74.3% (55/74) of the family members were carriers of heterozygous mutations. However, no significant difference was found in the 17-OHP levels between carriers and non-carriers (P>0.05).</p><p><b>CONCLUSION</b>There seems to be a specific spectrum of CYP21A2 gene mutations in Fujian area, where IVS2-13A/C>G and chimeras are the most common mutations.</p>

Risk factors of 125 cases of neonatal congenital hypothyroidism during perinatal period / 中华流行病学杂志

Objective To understand the relationship between perinatal factors and congenital hypothyroidism(CH)and provide scientific evidence for the prevention of CH. Methods A case-control study was conducted among 125 neonates with CH (case group) and 375 neonates without CH(control group)in Fujian Neonatal Screening Center from January in 2012 to December in 2013. Univariate and multivariate logistic regression analysis were performed to identify the risk factors to CH during perinatal period. Results Univariate logistic regression analysis indicated that compared with control group,gestational hypertension,gestational diabetes mellitus,gestational thyroid disease and older age of mother were the risk factors to CH,the difference was statistically significant (P<0.05) and the risk of CH was higher in female babies,preterm babies,post-term babies low birth weight babies,macrosomia,twins,babies with birth defects and infection in cases group than those in control group,the difference was statistically significant (P<0.05). Multivariate logistic analysis showed that older age of mother(OR=2.518,95%CI:1.186-5.347), gestational diabetes mellitus(OR=1.904,95%CI:1.190-3.045),gestational hypothyroidism or hyperthyroidism(OR=12.883 and 30.797,95%CI:2.055-80.751 and 3.309-286.594),preterm birth (OR=4.238,95%CI:1.269-14.155),and post-term birth(OR=12.799,95%CI:1.257-130.327),low birth weight(OR=3.505,95%CI:1.059-11.601),macrosomia(OR=3.733,95%CI:1.415-9.851), twin or multiparous delivery(OR=5.493,95%CI:1.701-17.735),birth defects(OR=3.665,95%CI:1.604-8.371)and fetal distress(OR=3.130,95%CI:1.317-7.440)were the high risk factors to CH (P<0.05). Conclusion CH was correlated with mother’s age,gestational diabetes,gestational thyroid disease as well as neonate’s birth weight and gestational age,foetus number,fetal distress and other complicated birth defects at certain degree. More attention should be paid to perinatal care to reduce risk factors and the incidence of CH.

Risk factors of 125 cases of neonatal congenital hypothyroidism during perinatal period / 中华流行病学杂志

Objective To understand the relationship between perinatal factors and congenital hypothyroidism(CH)and provide scientific evidence for the prevention of CH. Methods A case-control study was conducted among 125 neonates with CH (case group) and 375 neonates without CH(control group)in Fujian Neonatal Screening Center from January in 2012 to December in 2013. Univariate and multivariate logistic regression analysis were performed to identify the risk factors to CH during perinatal period. Results Univariate logistic regression analysis indicated that compared with control group,gestational hypertension,gestational diabetes mellitus,gestational thyroid disease and older age of mother were the risk factors to CH,the difference was statistically significant (P<0.05) and the risk of CH was higher in female babies,preterm babies,post-term babies low birth weight babies,macrosomia,twins,babies with birth defects and infection in cases group than those in control group,the difference was statistically significant (P<0.05). Multivariate logistic analysis showed that older age of mother(OR=2.518,95%CI:1.186-5.347), gestational diabetes mellitus(OR=1.904,95%CI:1.190-3.045),gestational hypothyroidism or hyperthyroidism(OR=12.883 and 30.797,95%CI:2.055-80.751 and 3.309-286.594),preterm birth (OR=4.238,95%CI:1.269-14.155),and post-term birth(OR=12.799,95%CI:1.257-130.327),low birth weight(OR=3.505,95%CI:1.059-11.601),macrosomia(OR=3.733,95%CI:1.415-9.851), twin or multiparous delivery(OR=5.493,95%CI:1.701-17.735),birth defects(OR=3.665,95%CI:1.604-8.371)and fetal distress(OR=3.130,95%CI:1.317-7.440)were the high risk factors to CH (P<0.05). Conclusion CH was correlated with mother’s age,gestational diabetes,gestational thyroid disease as well as neonate’s birth weight and gestational age,foetus number,fetal distress and other complicated birth defects at certain degree. More attention should be paid to perinatal care to reduce risk factors and the incidence of CH.

Association of thyroperoxidase gene polymorphisms with dyshormonogenesis in congenital hypothyroidism / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of thyroperoxidase (TPO) gene polymorphisms with dyshormonogenesis in congenital hypothyroidism (CH).</p><p><b>METHODS</b>The 17 exons and flanking introns of the TPO gene from 30 randomly selected samples were sequenced for the selection of single nucleotide polymorphisms (SNPs). In 136 patients with dyshormonogenetic CH and 141 healthy controls from the same region, the selected SNPs were genotyped by polymerase chain reaction (PCR) and direct sequencing or PCR-restriction fragment length polymorphism (RFLP).</p><p><b>RESULTS</b>Six SNPs (rs9678281, rs376413622, rs1126797, rs4927611, rs732609 and rs1126799) were selected to determine the genotype for each sample. Among these, rs4927611 and rs732609 showed a significant difference between the two groups in both allelic and genotypic frequencies. With a recessive model of inheritance, rs732609 CC (OR=0.484, 95%CI: 0.253-0.927, P=0.04) and rs4927611 TT (OR=0.32, 95%CI: 0.112-0.915, P=0.047) were greater in the patients.</p><p><b>CONCLUSION</b>rs4927611 and rs732609 may be associated with dyshormonogenetic CH. rs4927611 TT and rs732609 CC are genotypes associated with potential risk for the disease.</p>

Risk factors of 125 cases of neonatal congenital hypothyroidism during perinatal period / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the relationship between perinatal factors and congenital hypothyroidism (CH) and provide scientific evidence for the prevention of CH.</p><p><b>METHODS</b>A case-control study was conducted among 125 neonates with CH (case group) and 375 neonates without CH (control group) in Fujian Neonatal Screening Center from January in 2012 to December in 2013. Univariate and multivariate logistic regression analysis were performed to identify the risk factors to CH during perinatal period.</p><p><b>RESULTS</b>Univariate logistic regression analysis indicated that compared with control group, gestational hypertension, gestational diabetes mellitus, gestational thyroid disease and older age of mother were the risk factors to CH, the difference was statistically significant (P < 0.05) and the risk of CH was higher in female babies, preterm babies, post-term babies low birth weight babies, macrosomia, twins, babies with birth defects and infection in cases group than those in control group, the difference was statistically significant (P < 0.05). Multivariate logistic analysis showed that older age of mother (OR = 2.518, 95% CI: 1.186-5.347), gestational diabetes mellitus (OR = 1.904, 95% CI: 1.190-3.045), gestational hypothyroidism or hyperthyroidism (OR = 12.883 and 30.797, 95% CI: 2.055-80.751 and 3.309-286.594), preterm birth (OR = 4.238, 95% CI: 1.269-14.155), and post-term birth (OR = 12.799, 95% CI: 1.257-130.327), low birth weight (OR = 3.505, 95% CI: 1.059-11.601), macrosomia (OR = 3.733, 95% CI: 1.415-9.851), twin or multiparous delivery (OR = 5.493, 95% CI: 1.701-17.735), birth defects (OR = 3.665, 95% CI: 1.604-8.371) and fetal distress (OR = 3.130, 95% CI: 1.317-7.440) were the high risk factors to CH (P < 0.05).</p><p><b>CONCLUSION</b>CH was correlated with mother's age, gestational diabetes, gestational thyroid disease as well as neonate's birth weight and gestational age, foetus number, fetal distress and other complicated birth defects at certain degree. More attention should be paid to perinatal care to reduce risk factors and the incidence of CH.</p>