Objective: To investigate the clinical and molecular genetic features of neonatal congenital lipoid adrenal hyperplasia (CLAH) caused by mutations in steroidogenic acute regulatory protein (StAR) encoding gene. Methods: This study retrospectively analyzed the clinical data of a CLAH neonate admitted to Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University in April 2017. StAR gene was analyzed using high-throughput sequencing and Sanger sequencing. Relevant literature retrieved from databases including China National Knowledge Infrastructure (CNKI), Wanfang and PubMed were reviewed, and the reported cases with relatively complete clinical data and results of serum hormone test and StAR gene mutation analysis were collected. Results: The index patient presented with hyperpigmentation and growth retardation soon after birth. Laboratory tests revealed hyponatremia, hyperkalemia, increased serum adrenocorticotrophic hormone (263.4 pmol/L) and decreased 17-hydroxyprogesterone (0.16 ng/ml), dehydroepiandrosterone (<0.95 μmol/L), androstenedione (<1.0 nmol/L), testosterone (<0.025 ng/ml), progesterone (0.02 ng/ml) and cortisol (1.6 μg/ml). High-throughput sequencing showed that the patient carried a compound heterozygous mutation of p.Thr240fs in exon 6 and p.Gln258X in exon 7, inherited from the father and mother, respectively. Sanger sequencing confirmed the diagnosis of CLAH caused by StAR gene mutation. After steroid replacement therapy, the patient's symptoms resolved and the concentrations of electrolytes returned to normal. The neonate was followed up to two years of age and no abnormality was found in physical or neurological development. Two Chinese and 11 English publications were retrieved and altogether 96 cases of neonatal CLAH, including the index one, were reviewed and 42 of them had detailed clinical data. The most common clinical manifestations were skin pigmentation (85.7%, 36/42). Other manifestations included vomiting (35.7%, 15/42) and growth retardation (14.3%, 6/42). All patients with physical examination records had female external genitalia (100.0%, 35/35). The common laboratory abnormalities included hyponatremia (95.2%, 40/42), hyperkalemia (88.1%, 37/42), elevated serum adrenocorticotrophic hormone (100.0%, 37/37) and decreased 17-hydroxyprogesterone (90.5%, 19/21), cortisol (86.2%, 25/29), testosterone (9/10) and dehydroepiandrosterone (14/14). p.Gln258X was the most common StAR gene mutation in neonates in Eastern Asia, including China. Most cases had a good prognosis after appropriate steroid replacement. Conclusions CLAH should be considered for neonates with adrenocortical hypofunction, especially with female phenotypes and low 17-hydroxyprogesterone. Karyotyping and StAR gene analysis may be helpful in diagnosis. Timely and appropriate treatment could improve the prognosis.

Objective: To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 (GTF2IP23), in breast cancer and its effect on the host gene general transcription factor Ⅱi (GTF2I). Methods: The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results: The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues (P=0.007). The expression of GTF2IP23 was negatively correlated with GTF2I (r=-0.335, P=0.025). The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells (P<0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P<0.01). Overexpression of GTF2IP23 in ZR-75-30 cells significantly reduced the expression of GTF2I (P=0.034) and enhanced cell proliferation (P=0.017) and migration (P=0.026) capacity. Conclusions GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.

Objective To assess the association between three single nucleotide polymorphisms( SNPs) ( rs10878724、 rs7980829 and rs11177020 ) of lnc IFNG-AS1 and Hashimoto's thyroiditis ( HT) susceptibility. Methods TaqMan probe technology was used to genotype the selected SNPs in a total of 179 subjects, including 70 HT cases, and 109 controls. The expression levels of lnc IFNG-AS1 and IFNG were detected by SYBR-Green qRT-PCR. Results Compared with control, not only the A allele and AA genotype frequencies of rs10878724 were significantly different in group HT ( P=0. 01, P=0. 003), but also the T allele and TT genotype frequencies of rs7980829 were significantly high in group HT. Haplotype analysis showed that the G-G-A decreased the risk of HT (P=0.04), while the haplotype of A-T-T incresed the risk of HT( P=0.01). The relative expression of both IFNG mRNA and lnc IFNG-AS1 were higher in group HT than in control( P=0. 001,P=0. 013). In HT patients, IFNG mRNA relative expression in both rs7980829-TT and rs1087872-TT were significantly higher than those of other genotypes(P=0.017,P=0.009). Conclusion The SNPs of Inc IFNG-AS1 were correlated with the expression levels of IFNG and lncRNA IFNG-AS1. Noncoding genes should be further screened as potential biomarkers in prediction of HT susceptibility.

Objective To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 ( GTF2IP23), in breast cancer and its effect on the host gene general transcription factorⅡi (GTF2I).Methods The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real?time polymerase chain reaction (qRT?PCR).The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues ( P＜0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues ( P＝0.007). The expression of GTF2IP23 was negatively correlated with GTF2I ( r＝－0.335, P＝0.025).The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells ( P＜0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P＜0.01). Overexpression of GTF2IP23 in ZR?75?30 cells significantly reduced the expression of GTF2I (P＝0.034) and enhanced cell proliferation (P＝0.017) and migration (P＝0.026) capacity. Conclusions GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.

Objective To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 ( GTF2IP23), in breast cancer and its effect on the host gene general transcription factorⅡi (GTF2I).Methods The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real?time polymerase chain reaction (qRT?PCR).The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues ( P＜0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues ( P＝0.007). The expression of GTF2IP23 was negatively correlated with GTF2I ( r＝－0.335, P＝0.025).The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells ( P＜0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P＜0.01). Overexpression of GTF2IP23 in ZR?75?30 cells significantly reduced the expression of GTF2I (P＝0.034) and enhanced cell proliferation (P＝0.017) and migration (P＝0.026) capacity. Conclusions GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.

OBJECTIVETo explore clinical features and mutation types in patients from Fujian area with glutaric academia type I(GA I).

METHODSSerum 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.

RESULTSMutations 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.

CONCLUSIONc.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.

OBJECTIVETo assess the frequencies of CYP21A2 gene mutations among patients from Fujian area with classical 21-hydroxylase deficiency.

METHODSFor 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.

RESULTSEleven 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).

CONCLUSIONThere 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.

Adrenal Hyperplasia, Congenital ; genetics ; Alleles ; Female ; Humans ; Male ; Mutation ; genetics ; Steroid 21-Hydroxylase ; genetics

OBJECTIVETo understand the relationship between perinatal factors and congenital hypothyroidism (CH) and provide scientific evidence for the prevention of CH.

METHODSA 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.

RESULTSUnivariate 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).

CONCLUSIONCH 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.

Birth Weight ; Case-Control Studies ; Congenital Hypothyroidism ; epidemiology ; Diabetes, Gestational ; epidemiology ; Female ; Gestational Age ; Humans ; Hypertension, Pregnancy-Induced ; epidemiology ; Incidence ; Infant, Newborn ; Infant, Premature ; Maternal Age ; Neonatal Screening ; Pregnancy ; Pregnancy Complications ; epidemiology ; Premature Birth ; Risk Factors ; Twins

OBJECTIVETo assess the association of thyroperoxidase (TPO) gene polymorphisms with dyshormonogenesis in congenital hypothyroidism (CH).

METHODSThe 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).

RESULTSSix 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.

CONCLUSIONrs4927611 and rs732609 may be associated with dyshormonogenetic CH. rs4927611 TT and rs732609 CC are genotypes associated with potential risk for the disease.

Alleles ; Autoantigens ; genetics ; Base Sequence ; Child, Preschool ; Congenital Hypothyroidism ; blood ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Infant ; Infant, Newborn ; Iodide Peroxidase ; genetics ; Iron-Binding Proteins ; genetics ; Linkage Disequilibrium ; Male ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Risk Factors ; Thyrotropin ; blood ; Thyroxine ; blood

OBJECTIVETo study the characteristics of phenylalanine hydroxylase gene (PAH) mutations in patients with PAH deficiency in Fujian population.

METHODSPeripheral blood samples of 36 patients and their parents with classical type phenylketouria (PKU) were collected. Genomic DNA was extracted. Following PCR amplification, DNA sequencing was carried out to identify the origins of mutations.

RESULTSTwenty types mutations were identified in 63 of the 72 alleles. The most common mutations were R241C, R408Q and Ex6-96A>G, which respectively accounted for 15.9%, 12.7% and 11.1% of all mutant alleles. The c.189_190dupTGAC mutation was first reported. R241C was associated with 28% of mild hyperphenylalaninemia and R408Q is associated with 25% of classical PKU.

CONCLUSIONThere is a specific spectrum of PAH gene mutation in Fujian region. R241C, R408Q and Ex6-96A>G are the most common mutations.

Adolescent ; Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Child, Preschool ; China ; Female ; Genotype ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Phenylalanine Hydroxylase ; genetics ; Phenylketonurias ; enzymology ; genetics