Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China / 대한소아소화기영양학회지

Purpose@#Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. @*Methods@#We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. @*Results@#Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. @*Conclusion@#The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

Analysis of thyroid stimulating hormone receptor gene mutation in children with hyperthyroidism / 中华内分泌代谢杂志

Objective To explore the characterization of thyroid stimulating hormone receptor(TSHR) gene mutational spectrum in children with hyperthyroidism from Guangzhou. Methods Ninety children were diagnosed with hyperthyroidism from July 2009 to July 2014 in our institute. Their median age at diagnosis was(7.5± 3.4) years, and there were 28 males and 62 females. Mutational analysis were performed by performing polymerase chain reaction (PCR) and DNA direct sequencing of exon 10 of TSHR gene. TSHR gene mutations from 50 unrelated healthy children were served as controls. The correlation between TSHR gene and hyperthyroidism in children was explored. Results A total of 3 mutations were identified in ninety children who were diagnosed with hyperthyroidism, one synonymous mutations(p.V614V), and two missense mutations( p. R707W and p. D727E). Mutation of p. V614V do not change amino acid and do not influence the structure and function of TSHR, no pathogenicity. p.R707W is a SNP associated with human cancers. The frequency of C allele of the D727E in children with hyperthyroidism was 86.7%, while 55.0% in the controls, significant different between the children with hyperthyroidism and the controls( P＜0. 01). In this study, a very high association between the D727E SNP and hyperthyroidism ( OR=18. 86, P＜0. 01) was found. Conclusion Three different mutations of TSHR gene exon 10 were identified in 90 children with hyperthyroidism, (c.1842A＞G,p.V614V、c.2119C＞T,p.R707W、c.2181G＞C,p.D727E), there were association between p.D727E and hyperthyroidism, nor p. V614V and p. R707W. Finally, p. D727E may be correlated with hyperthyroidism in children.

Clinical research on methimazole treatment of 379 children with hyperthyroidism at a single institution / 中华内分泌代谢杂志

Objective To investigate the clinical efficacy and adverse events of methimazole ( MMI ) treatment for children with hyperthyroidism, and to identify the predictors of remission and relapse. Methods A total of379children(260girlsand119boys)diagnosedwithhyperthyroidismandtreatedbyMMIinGuangzhouWomenand Children's Medical Center from March, 2004 to July, 2014 were retrospectively analyzed. The average age at diagnosiswas(9.3±2.3)years(range2.0~15.9years). Results AftertreatmentwithMMIfor3and6months, the thyroid functions of 96. 3%(365/379) and 98. 9%(375/379) patients returned to normal, respectively. By the end of this study, 256(67. 5%) patients continued to use MMI treatment and 44 patients(11. 6%) dropped out. 79 patients(20. 8%) achieved remission, 35 patients (44. 3%) of whom experienced a later relapse. Children who achieved constant remission had significantly lower FT3 and FT4 levels at diagnosis compared with the relapsed children(P<0. 05 or P<0. 01). It was more likely to remain long-term remission for children turned to be euthyroid within 3 months after initiating MMI treatment(P<0. 05). The relieved patients with family history of thyroid diseases weremorelikelytoberelapsed(P<0.05). Therewerenosignificantdifferencesinage,gender,exophthalmos, initial goiter size, thyroid peroxidase autoantibody, and thyroglobulin antibody levels between the relieved and relapsed patients. The overall incidence of adverse events associated with MMI was 27. 7%, mainly elevated alanine aminotransferase, bilirubin, and neutropenia. Most(66. 7%) of adverse events occurred within the first three months of MMI treatment. Conclusion MMI has a good effect on pediatric hyperthyroidism, with low remission and high relapse rate. The low thyroid hormone concentrations at diagnosis and normalization of thyroid function within three months seem to be useful predictors of remission. Vigilance is needed concerning MMI-associated adverse events throughout the MMI treatment period, especially during the first trimester of MMI initiation.

Progress in the correlation between thyroid stimulating hormone receptor gene and hyperthyroidism / 中华实用儿科临床杂志

The cause of hyperthyroidism is still not clear.Thyroid stimulating hormone receptor(TSHR) gene is one of the hot topic genes in the etiology of hyperthyroidism.In this review paper,the progress of correlation between TSHR gene and hyperthyroidism was summarized.Results suggested that TSHR gene germline mutations could cause familial non-autoimmune autosomal dominant hyperthyroidism and persistent sporadic congenital non-autoimmune hyperthyroidism.In addition,TSHR gene mutation may also undermine the stability of the TSHR and then become the autoantigens to make producing TSHR antibodies.Which can stimulate thyroid follicular to secrete excessive thyroid hormone and then cause Graves' disease.However,the relationship between TSHR gene and the pathogenesis of Graves' disease still needs further study.

Clinical and molecular characteristics of 27 children with Prader-Willi syndrome in South China / 中华实用儿科临床杂志

Objective To understand the clinical and molecular characteristics of children with Prader-Willi syndrome (PWS) in South China.Methods Clinical and molecular data of children diagnosed as PWS by Methylation-specific PCR(MS-PCR) and/or Array Comparative Genomic Hybridization(Array-CGH)in Guangzhou Women and Children's Medical Center from November 2012 to November 2014 were analyzed.Results A total of 27 children diagnosed as PWS were included in this study,including 21 cases diagnosed by Array Comparative Genomic Hybridization (Array-CGH) and 13 cases diagnosed by methylation-specific PC R (MS-PCR).Within the 27 cases,13 cases were male(48.1％) and 14 cases were female(51.9％).The age on diagnosis was from 16 days to 16 years old.MS-PCR was performed in 13 cases,7 cases of them also performed Array-CGH,both of them showed a 174 bp fragment from the methylated allele and a 100 bp fragment from the unmethylated allele.Array-CGH analysis was performed in 21 cases,paternal deletion in 18 cases and mean interstitial deletions measure (5.48 ± 0.51) Mb in size,paternal duplication in 2 cases,loss of heterozygosity measure approximately 79.58 Mb in 1 case.Eighteen simple chromosome deletion cases were divided into 6 Del Ⅰ and 12 Del Ⅱ according to the location of Array-CGH and query the database to DECIPHER(Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources).The major phenotype included central hypotonia and feeding difficulty in all cases (100.0％),hypogonadism in 25 cases (92.6％),weak crying in 22 cases(81.5％),and hypopigmentation in 22 cases(81.5％).Fourteen cases beyond 1 year old had varied degrees of development disability and behavioral and psychiatric disturbance:speech articulation defects in 13 cases(92.9％),hyperphagia and weight gain too fast in 13 cases(92.9％) when they were between 1 to 6 years old[(2.80 ± 1.32) years old],and obesity in 12 cases (85.7％).Conclusions For PWS children in South China,there is no statistically significant difference in the clinical manifestation between Del Ⅰ and Del Ⅱ.PWS children in South China have typical clinical characteristics,which can be used as a further screening indication to implement molecular diagnostics.

Analysis of clinical features and arylsulfatase B gene mutation in thirteen Chinese children with mucopolysaccharidosis type VI / 中华儿科杂志

<p><b>OBJECTIVE</b>Mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome is an autosomal recessive lysosomal storage disease caused by a deficiency of arylsulfatase B(ARSB), which is required in the degradation of dermatan sulfate and chondroitin sulfate. The deficiency of ARSB leads to an accumulation of dermatan sulfate and chondroitin sulfate in lysosomes and gross excretion in the urine.Few articles about clinical study and ARSB gene mutation analysis of Chinese MPS VI patients were published. This study aimed to explore the clinical features and characteristics of ARSB gene in Chinese children with MPS VI.</p><p><b>METHOD</b>Thirteen children were diagnosed as MPS VI by ARSB enzyme activity determination during the period from 2009 to 2013. Their clinical features, radiological findings and urine glycosaminoglycan (GAG) levels were retrospectively reviewed. Direct sequencing was used to identify any mutation in the ARSB gene.</p><p><b>RESULT</b>Thirteen children were diagnosed at the average age of (3.9 ± 2.2) years with 6 male and 7 female. All of these children presented with severe form and onset at an early age of (1.5 ± 0.8) years.Other clinical features included coarse facies, short stature, skeleton deformity, corneal clouding, hepatosplenomegaly with normal intelligence. The radiological findings in all children were characteristic of dysostosis multiplex, like abnormal development of vertebral bodies of the spine, campylorrhachia and paddle-shaped widened ribs. The MRI in case 2 showed cervical cord compression and multiple cysts degeneration in the corona radiate, cella lateralis and callosum.High urine GAG levels were detected, (307.10 ± 112.14) mg/L (Normally below 70 mg/L) and (722.28 ± 245.68) µg/mg creatinine. The ARSB enzyme activity in leukocytes was low, (13.29 ± 6.22) nmol/(mg×h) [Normal range (47-169) nmol/(mg×h)] by fluorogenic assay and (0.24 ± 0.18) U/g [Normal range (1.01-11.47) U/g] by colorimetric assay. A total of 11 mutations were identified by molecular analysis, including seven previously reported mutations (p.L72R, p.G167R, p.G303E, p.F399L, p. T442M, p.Y255X and p.R327X) and four novel mutations (p.Y175D, p.S403X, p.S464X and large deletion including ex. 2, 3). The c.1197C>G (p.F399L) mutation was the most common mutation in this study (31%).</p><p><b>CONCLUSION</b>The severe form of MPS VI is characterized by early onset and rapid illness progression. Both the radiological findings and increased urine GAG are important clues to diagnose MPS VI.Large decrease or absence of ARSB activity is diagnostic for MPS VI.Four novel mutations of ARSB gene were identified. The reported mutation c.1197C>G (p.F399L) was the hot-spot mutation in this study.</p>

Analysis of two cases of Turner syndrome with 45,X/46,XY karyotype / 南方医科大学学报

We report two cases of Turner syndrome with a female phenotype and a 45,X(22)/46,XY(88) karyotype. The relevant literatures in relation to the incidence, pathogenesis, clinical manifestations and managements of Turner syndrome with a 45,X/46,XY karyotype were reviewed.

Analysis of pathogens of pneumonia in children based on association rules / 生物医学工程学杂志

The present paper was aimed to study the relationship between the pneumonia clinical features and the pathogens of pneumonia in children by making use of association rules based on the clinical data of 6 300 cases of pneumonia. Through software analysis, the different association relationship can be obtained between different clinical features of pneumonia in children, such as gender, age and region, etc., and the pathogens of pneumonia. For example, children of different sex with the same pathogen showed different association relationships. Due to the different association relationships between the pneumonia clinical features and the pathogens of pneumonia in children of Guangzhou area, different methods in prevention and treatment of children's pneumonia should be adopted according to actual condition, in order to achieve the best results.

Epidermal growth factor concentrations in human milk, cow's milk and cow's milk-based infant formulas / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Because maternal epidermal growth factor (EGF) may be an adaptive response to accelerate growth and maturation in premature infants, we compared the EGF content in fresh cow's milk and cow's milk-based infant formulas with full and preterm mother's milk.</p><p><b>METHODS</b>EGF content of 57 human colostrum from mothers delivering prematurely and at term, 4 different fresh cow's milk and 8 different cow's milk-based infant formulas was determined by radioimmunoassay (RIA).</p><p><b>RESULTS</b>Human milk from mothers of premature infants had a higher EGF content compared to that from mothers of term infants (28.2 +/- 10.3 nmol/L vs. 17.3 +/- 9.6 nmol/L). EGF content in human milk negatively correlated with gestational age and birth weight of neonates. EGF content in fresh cow's milk (13.8 - 18.2 nmol/L) was similar to that in human term milk. EGF levels in non-hydrolyzed protein formulas were much lower (5.6 - 8.6 nmol/L), and were undetectable in hydrolyzed protein formulas.</p><p><b>CONCLUSION</b>The high EGF content in premature milk may represent a maternal compensatory mechanism to accelerate the growth and development of immature infants. Feeding infants with breast milk from their own mother should be advocated since there is lack of EGF in cow's milk-based infant formulas.</p>

Epidermal growth factor contents in human milk, cow's milk and cow's-milk-based infant formulas / 中国病理生理杂志

AIM: To determine EGF contents in human milk, frech cow's milk and cow's milk-based infant formulas and the relationship between EGF content of human milk and neonatal maturity.METHODS: EGF contents in 57 human colostrum from mothers delivering prematurely and at term, 4 different fresh cow's milk and 8 different cow's-milk-based infant formulas with hydrolyzed and non-hydrolyzed proteins were determined by radioimmunoassay (RIA). RESULTS: Human milk from mothers of premature infants had higher EGF content compared to that from mothers of term infants[(28.2?10.3) nmol/L vs(17.3?9.6) nmol/L]. There was a negative correlation between EGF content of human milk and gestational age, birth weight of neonates. The values in fresh cow's milk [(16.6?3.8) nmol/L]were similar to that in human term milk. The contents in non-hydrolyzed protein formulas[(7.5?1.9) nmol/L]were much lower than that in human milk and fresh cow's milk. No immunoreactive EGF was detected in all hydrolyzed protein formulas. CONCLUSION: The occurrence of high EGF concentration in premature milk may represent a maternal compensatory mechanism to accelerate the growth and maturation in immature infants. Lack of EGF in formulas suggests that they may not suitable for those newborns with immature or damaged gastrointestinal tract.