Maternal phenylketonuria(MPKU) is a syndrome caused by high phenylalanine concentrations in serum of pregnant women with phenylketonuria.MPKU results in neonatal microcephaly,facial dysmorphism,congenital heart defects,mental retardation,intrauterine growth restriction,behavior and emotional problems.To control serum Phe level of pregnant phenylketonuria women and maintain Phe concentration between 120 to 360μmol/L will prevent offspring poor outcomes such as intellectual disabilities and microcephaly.Three level interventions are best ways in MPKU management.

Adrenoleukodystrophy (ALD,OMIM# 300100) is one of the most common peroxisomal disease.It is a kind of X-linked genetic disorder.The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal membrane protein(ALDP).A defect in ALDP results in very long-chain fatty acids can not be transported from the cytosol into the peroxisome and impaired accumulation of very long chain fatty acid (VLCFA)-CoA esters in the white matter of the brain,the spinal cord and adrenal cortex.The clinical spectrum in males with X-ALD ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination.Corticosteroid replacement therapy is essential and life saving treatment,bone marrow transplantation (BMT) is an option for boys and adolescents in early stages.This review focus on the genetic pathology,diagnosis and managements of patients with X-ALD and provides a guideline for clinicians.

Biomarkers ; blood ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Male ; Prader-Willi Syndrome ; diagnosis ; genetics ; pathology ; therapy

Objective: To develop a molecular screening test for genetic defects on hearing loss related genes has significant impacts on early identification of hereditary hearing loss and genetic susceptibility to aminoglycoside ototoxicity. Early identification of pre-lingual hearing loss is very important for patient's language development, academic achievement, and social skill. Two common mutations, the 235delC in GJB2 gene and the mutation A1555G in mitochondrial DNA, are included in the newly developed screening panel for Chinese population. Methods: A molecular genetic assay, based on fluorescent labeled multiplex PCR and automatic DNA fragment analyzing techniques, was developed to detect both mutations simultaneously. Results: This assay was able to detect both mutations from patient's samples, and pooled DNA tests, as well as suitable to detect mutation from the DNA extracted from dried blood spot and buccal swab. Conclusion: This assay could be a useful tool for newborn screening and carrier screening for the hereditary hearing loss for the Chinese population.

Objective By using array-based single nucleotide polymorphisms comparative genomic hybridization (SNP-aCGH) to detect and fine mapping copy number variations (CNVs) in children with unexplained mental retardation/brain development delay(MR/BD),then the CNVs were analyzed to determine diagnosis and offer genetic counseling,finally to discuss the application of SNP-aCGH in genetic diagnosis of MR/BD with unknown causes.Methods Ninety-two children with unexplained MR/BD were recruited.SNP-aCGH was used to get CNVs from the whole genome-wide,and the correlation of CNVs and phenotype was analyzed to definit disease genes or pathogenic fragment.Statistics was performed to analyze the common phenotype between positive cases (case with CNVs) and negative cases.Results (1) The CNVs were detected in 10 cases with a detection rate of 10.86％,from which 8 cases showed subtelomeric aberration,5 cases without subtelomeric aberration,and the rate was 8.70％,5.40％,respectively.The CNVs related to MR/BD involved 10 different subtelomeric regions (9p,21q,3p,2p,15q,4p,12p,22q,16p,17p),and 7 different regions without subtelomeric (1p,4q,2p,14q,15q,12q,22q).The deletions involved 11 zones (size:1.05-8.80 Mb),and duplications referred to 8 zones (size:1.33-31.25 Mb).(2) One case was diagnosed as 9p duplication syndrome,for candidate genes:DOCK8,VLDLR.A case was detected with a gene fracture (CRBN).One case was diagnosed as Coffin-Sirrs syndrome combined with a deletion of 15q26.3-qter,for candidate genes:SOX11 and LINS1,respectively.One case referred to 12p13.3 deletion syndrome,for candidate genes:ELKS,ERC1.One case referred to 22q13.2-qter deletion,for candidate genes:SHANK3.Two cases were diagnosed as ATR-16 syndrome with 17p13.3 deletion syndrome,their candidate genes:HBA1,HBA2,SOX8 for the former,YWHAE,LIS1 for the latter.(3)There were statistically significant differences in comparison of positive cases to the negative ones for growth delay,internal organs deformity,low birth weight infant(LBW) and premature infant (all P ＜0.05).Conclusions (1) Besides MR/BD in different degrees in all the positive cases,they also showed growth delay,a portion of them with internal organs deformity,low birth weight infant and premature infant.(2) Subtelomeric aberrations are related to MR/BD,while the submicroscopic rearrangement in regions without subtelomeric is suspiciously pathogenic,and need to be further studied.(3) SNP-aCGH can fine mapping the region of CNVs by high resolution from the whole genome-wide,which does contribute to limit the zones for finding pathogenic region and candidate genes,as well as to offer a technology platform for investigating about the correlation of phenotype and genes or CNVs.

Objective To analyze the genotype-phenotype correlations of Angelman syndrome ( AS ) , and to discuss the advantage of applying array-based single nucleotide polymorphisms comparative genomic hybridization ( SNP aCGH) in diagnosis of AS. Methods Examination of electroencephalogram( EEG) and intelligence quotient( IQ) evaluation were done for 11 cases diagnosed as AS clinically. Gesell scares were chosen as the evaluation criterion of IQ. The screening techniques was methylation polymerase chain reaction( MS-PCR) ,then SNP aCGH was used to make genetic diagnosis. Results (1)Eleven cases of AS were confirmed:1 case had UPD(uniparental disomy),10 cases were type of deletion, from which 6 cases were deletion (Ⅱ) , 4 cases were deletion (Ⅰ) . ( 2 ) The copy number variations were detected in the region of 15q11-q13,which contained genes like MKRN3,MAGEL2,NDN,SNRPN, SNURF,GABRB3,GABRA5,GABRG3,UBE3A,OCA2,ATP10A. To search online Mendelian inheritance in man,genes above were correlated with AS manifestation. (3)All cases of deletion were 3-5 standard deviation(SD) in weight and height to normal children at the same age and with the same sex,while UPD was below 1. 5 SD. Gesell scares showed that the deletion(Ⅰ) was the most serious in mental retardation,deletion(Ⅱ) was moderate,and the UPD was mild. Eight cases were hypopigmentation,and one was the UPD. EEG revealed that 1 case of deletion(Ⅰ) and the UPD were spike occasionally,another one deletion(Ⅰ) was limit EEG. The rest cases displayed slow and spike waves paroxysmal-ly,with amplitude of medium or high,2. 5-3. 0 Hz. Conclusions Not only can SNP aCGH make a diagnosis of AS but discriminate the types of genetic pathology. Since different type contributes to a diverse of clinical features and the rate of recurrence is also different,it is significant for family genetic consultation. Moreover,the technology is advantageous for the study on the pathogenesis and gene function.

Objective To establish the co-culture model in vitro and induce bone marrow mesenchymal stem cells (MSCs) to differentiate into lung alveolar epithelial cells. Methods Each group had 6 samples, control group was MSCs alone; Group A was the MSCs cultured with the cells from normal lung; and Group B was the MSCs with the cells from injuried lung. Each group was cultured for 8 days and the two markers of lung alveolar epithelial cells including AQP5 and SP-C were tested by laser confocal microscopy and RT-PCR. Results Only AQP5 was detected in the control group and Group A, both AQP5 and SP-C were detected in Group B, the AQP5 mRNA expression in Group B was significantly increased compared with that in the control group(P<0.01). The AQP5 mRNA expression in Group B was also significantly increased compared with that in Group A (P<0.01). But there was no significant difference in AQP5 mRNA expression between Group A and control group. Conclusion We have successfully established the co-culture model in vitro to induce bone marrow mesenchymal stem cells to differentiate into lung epithelial cells.

Objective To investigate the outcomes of unselected peripheral T cell lymphoma (PTCL) patients treated with in-tensive first-line chemotherapy with high-dose therapy followed by autologous stem cell transplantation (ASCT).Methods Here a nonrandom study was reported for 23 PTCL patients treated with first-line intensive chemotherapy followed by autologous stem cell trans-plantation and 23 PTCL patients treated with conventional chemotherapy during January in 2000 to 2011 .All patients had received E-CHOP for 6~8 cycles, and autologous stem cell transplantation group was administrated with intensive chemotherapy followed by ASCT after complete remission or partial remission .Results There was no statistically significant difference in short-term therapeutic effect between two groups( P >0.05), but the 5-year overall survival(OS) of autologous stem cell transplantation group( 58%) was higher than conventional chemotherapy group , as well as 5-year disease-free survival time (DFS) (45%in autologous stem cell transplanta-tion group, and 21%in conventional chemotherapy group ) with both statistical significance ( P <0.05).Only the incidence of Ⅳ° myelosuppression in autologous stem cell transplantation group ( 100%) was higher than that in conventional chemotherapy group ( 13%) ( P <0.01 ) .Conclusions First-line intensive chemotherapy followed by autologous stem cell transplantation for peripheral T cell lymphoma was quietly safe utility , it was better than conventional chemotherapy which would be considered as first -line method.

In recent years, genetic analysis technology has been widely used in diagnosis of complex and difficult disease, neonatal and high-risk population disease screening, pre-implantation diagnosis, risk assessment of genetic disease recurrence and gene therapy.Clinicians need to better understand the purpose and timing of using genetic analysis technology, only understand the advantages and limitations of these technologies, the genetic analysis technology can be truly applied to clinical practice, it is helpful to improve the ability and level of diagnosis and treatment of here-ditary diseases.

Hypoglycemia is a common metabolic disorder in children,and its incidence is about 10％.Among them,the incidence of hereditary related diseases is about 1/30 000-10/30 000.More and more genetic diseases leading to hypoglycemia have been discovered in recent years.Children with the disease may have mild nervous system damage at the earliest stage,and liver encephalopathy,respiratory failure,confusion or even death in severe cases.Therefore,more and more attention has been paid to the study of hypoglycemia related genetic diseases,but the diagnosis and differential diagnosis of hypoglycemia has not yet formed an unified consensus.Now,the diagnosis and treatment of this kind of related diseases were summarized in order to provide data for clinical practice.