Clinical and genetic analysis of 14 cases with 21-hydroxylase deficiency / 中华实用儿科临床杂志

Objective To analyze the correlation of clinical phenotype and genotype and gene mutation frequency characteristics of 21-hydroxylase deficiency,and to provide the basis for clinical diagnosis and methods for early intervention.Methods The clinical phenotypic signs and examination results of 14 cases with 21-hydroxylase deficiency were collected from September 2008 to December 2016 in Children's Hospital of Shanxi Province.Point mutations,deletions and conversion mutations for gene CYP21A2 coding 21-hydroxylase were detected through using next generation sequencing(NGS) and multiplex ligation-dependent probe amplification (MLPA).The captured mutations were further confirmed with Sanger sequencing.Furthermore,the family members underwent the co-segregation validation through the Sanger sequencing or MLPA in those captured mutated sites.Results Among the total 14 cases,9 cases were identified as the salt wasting,5 cases the simple virilizing;10 cases of compound heterozygous mutations,and 4 cases of homozygous mutations.Analysis of the 14 patients revealed 8 different kinds of mutations in CYP21A2 gene.The most frequent mutations of CYP21A2 gene were I2G [50％ (14/28)] and I173N [21.4％ (6/28)],followed by Arg357Trp[10.7％ (3/28)].Del[10.7％ (3/28)] mutations including E247fs,Gly1 1 1fs and R484fs.Q319X [3.6％ (1/28)] and Arg355His[3.6％ (1/28)] were rarely found.Missense mutation was found in 10 cases,splicing mutation in 14 cases,frameshifi mutations in 3 cases,nonsense mutations in 1 case.All of the mutations were inherited from their parents,and no new mutation was found.The most common mutations for salt wasting and simple virilizing were respectively I2G[50％ (9/18)] and I173N [50％ (5/10)].Collectively,genotypes and phenotypes were matched with each other.Conclusions The combination of clinical phenotypes with laboratory examination by gene sequencing and comprehensive analysis,is helpful to early diagnosis,differential diagnosis and optimized treatment,which will improve prognosis and provide guidance for genetic consultancy.

Levels of phthalate internal exposure levels in pregnant women and influencing factors / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age ≤ 16 weeks).</p><p><b>METHODS</b>During April to June in 2013, 1 020 pregnant women (gestation age ≤ 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors.</p><p><b>RESULTS</b>The detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253-0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732).</p><p><b>CONCLUSION</b>Pregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different.</p>

Clinical and genetic analysis for a Joubert syndrome family with CC2D2A gene mutations / 中华儿科杂志

<p><b>OBJECTIVE</b>To confirm the genetic diagnosis for providing services for genetic counseling and prenatal diagnosis, we analyzed the clinical and genetic data of a pedigree which is clinically diagnosed as Joubert syndrome.</p><p><b>METHOD</b>A Joubert syndrome pedigree was enrolled as subject of this study from our hospital's outpatients in 2013. Following the medical history collection of the proband and the suffering fetus, target sequence capture and the next-generation sequencing technology were used for the proband and the suffering fetus to find the causative genes and sanger sequencing for the members of the pedigree to check and verify if the inherited mutations are in accordance with the Mendelian inheritance. Combining the clinical symptoms and signs with the total testing results, we analyzed the Joubert syndrome pedigree clinically and genetically.</p><p><b>RESULT</b>The proband showed abnormal respiratory patterns (neonatal tachypnea) and hypertonia without abnormal eye movements, and reflected the molar tooth sign on the magnetic resonance imaging. And afterwards the patient developed hypotonia, ataxia, growth and intellectual disability accompanied by congenital blepharoptosis. There were no any symptoms and signs of liver, kidney and eyesight abnormalities so far. The affected fetus showed hydrocephalus by the auxiliary examination during the second trimesters of pregnancy without any appearance deformities. Both the proband and the affected fetus carried a missense mutation of CC2D2A gene c.2999A > T (p.Glu1000Val) from their father and carried the deletion of exon 20-21 on the same gene. Both variations were confirmed to be the Mendelian genetic compound heterozygous pattern. Whereas, the missense mutations c.2999A > T (p.Glu1000Val) on the CC2D2A gene have been proved to be inherited from the proband's father and the proband as well as the affected fetus. However, the proband's mother was normal at this locus of CC2D2A gene. The missense mutations c.2999A >T (p.Glu1000Val) have been confirmed to accord with Mendelian inheritance.</p><p><b>CONCLUSION</b>The Joubert syndrome patient may show hypertonia in the early postnatal days as a result of hydrocephalus during the second and third trimesters of pregnancy besides manifesting hypotonia, ataxia, growth and intellectual disability markedly with age accompanied by the congenital blepharoptosis and revealing the molar tooth sign on the magnetic resonance imaging, considering the medical history and the whole testing results, the compound heterozygous mutations of c.2999A > T (p.Glu1000Val) and deletion of exon 20-21 of CC2D2A gene in the pedigree may be the causal gene mutations.</p>

Genetic and prenatal diagnosis for a Chinese family with primary carnitine deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of SLC22A5 gene in a 5-month-old boy affected with primary carnitine deficiency and provide genetic counseling and prenatal diagnosis for the members of his family.</p><p><b>METHODS</b>DNA was extracted from peripheral blood samples derived from the proband, his parents and elder sister, as well as amniotic fluid from his pregnant mother. All of the 10 exons of the SLC22A5 gene were amplified by PCR and subjected to Sanger sequencing. The amniotic fluid sample was also subjected to G-banded karyotyping and multiplex ligation-dependent probe amplification (MLPA).</p><p><b>RESULTS</b>A homozygous mutation c.760C>T (p.R254X) of the SLC22A5 gene was detected in the proband. Heterozygous mutation c.760C>T (p.R254X) was also found in other family members including the fetus. The karyotyping and chromosomal microdeletion testing for the amniotic fluid sample were both normal.</p><p><b>CONCLUSION</b>The newly identified homozygous nonsense c.760C>T (p.R254X) mutation of the SLC22A5 gene probably underlies the primary carnitine deficiency of the proband. Genetic counseling and prenatal diagnosis have been provided for this family.</p>

Protection role of taurine transporter in rats brain edema followed severe traumatic head injury / 天津医药

Objective To investigate the effect of taurine transporter in the process of protection of brain edema in rats with severe traumatic head injury. Methods A total of 24 Male Sprague-Dawley rats were randomly divided into 4 groups. Except the control rats (Group Sham), all other three groups were subjected to lateral fluid percussion head injury. The TBI (Traumatic brain injury) models (Group TBI) and surgical control rats (Group Sham) were injected with saline through caudal vein after surgery, while the Taurine prevention and Taurine treatment models (Group Pre Tau and Group Tau) were injected with 120 g/L taurine solution before or after surgeries respectively. Water content in each brain, mRNA and protein expres?sion of aquaporin 4 and taurine transporter in the injured rat brain hemispheres were all evaluated over the time course of the study (7 d) in each group. Results Compared with rats in Group Sham, water content in each brain increase, mRNA tran?scription and protein expression of AQP4 were both up regulated but the mRNA transcription and protein expression of TauT were both down-regulated in rats in TBI group. Compared with rats in TBI group, brain water content, mRNA transcription and protein expression of AQP4 all decrease while mRNA transcription and protein expression of TauT all increase in rats in Pre tau and Tau groups. There is no statistical difference of TauT expression between rats in pre-tau group and Tau group. Conclusion Taurine exert its neuron protection role through draining water content from brain and down regulating expres?sion of AQP4 but rising expression of TauT after TBI.

Exposure risk assessment of plasticizer in dietary food in Xiamen / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the dietary consumption of residents in Xiamen and the content of phthalic acid esters (PAEs) in food, and to assess the plasticizer exposure risk of diet in Xiamen.</p><p><b>METHODS</b>The survey was conducted by stratified cluster random sampling method in Xiamen from September to October in 2010. According to the Xiamen administrative division, six neighborhood communities were selected as sampling units, then 25 families were randomly chosen from each sampling units.From the above 150 families, the permanent residents over the age of six were permitted to our study. The survey included 495 residents totally. These participants' information, such as basic personal information, physical activity levels, meal frequency and the average consumption of 33 kinds of food in 13 categories were collected using questionnaires. Thirteen categories included cereal and tubers, beans, vegetables, fungi and algae, fruits, dairy products, meat, seafood, eggs, snacks, beverages, cooking oil and spices. The height and weight of residents were measured and the average daily dietary intake was calculated. Thirty-three kinds of food in 13 categories were collected in supermarkets in Xiamen. According to the annual sales ranking, the top three-five brands of each kinds of food were selected and numbered, then two or three brands were chosen by random number table method from them; three completely individual packed samples in the same batch of each brand were detected; 243 samples were included in our study.100-500 g solid samples or 100-500 ml liquid samples were collected. The content of diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) in food were detected by liquid chromatography mass spectrometry, which expressed by median (minimum-maximum). The exposure dose, contribution rate and risk index of PAEs were calculated by point estimation method.</p><p><b>RESULTS</b>According to the average daily dietary intake of residents in Xiamen, the top three ones in 13 categories of food were cereal and tubers (337.16 g/d, 18.21%), vegetables (309.12 g/d, 16.69%) and fruits (213.20 g/d, 11.51%). The content of DEP, DBP or DEHP among different categories of food was significantly different (χ² values were 58.05, 50.19 and 102.10, P < 0.01). Among 13 categories of food, seafood contained the most DEP (0.090 (0.000-0.324)mg/kg); cooking oil had the most DBP (0.700(0.000-2.980) mg/kg) and DEHP (5.115(0.000-24.160) mg/kg). DEP, DBP and DEHP exposure(0.19, 4.20, 18.10 µg × kg⁻¹ ×d ⁻¹)in dietary food in Xiamen were less than the reference dose(RfD) (800, 100, 20 µg × kg⁻¹ × d⁻¹) proposed by the United States Environmental Protection Agency (EPA), and the risk indexes were 0.02%, 4.20% and 90.50%, respectively. Among 13 categories of foods, seafood was the main source of DEP dietary exposure. The exposure dose and contribution rate of DEP in seafood were 0.18 µg × kg⁻¹ × d⁻¹ and 94.74%, respectively.Vegetables were the main source of DBP and DEHP dietary exposure. The exposure dose and contribution rate of DBP and DEHP were 1.48 µg × kg⁻¹ × d⁻¹, 35.24% and 6.07 µg × kg⁻¹ × d⁻¹, 33.54%, respectively.</p><p><b>CONCLUSION</b>The food consumed by residents in Xiamen was overall in a safe state, but to some extent, there still exists DEHP exposure risk in foods.</p>