The expression and significance of circulating microRNA of rats with hypobaric hypoxia-induced pulmonary hypertension / 西安交通大学学报(医学版)

Objective To investigate the expression of circulating microRNA (miRNA) of rats with hypobaric hypoxia‐induced pulmonary hypertension (HPH) .Methods Commercial rat miRNA microarray was employed to detect and analyze the circulating miRNA profile in the serum samples of Sprague‐Dawley rats with hypobaric hypoxia‐induced HPH and controls .Furthermore ,differentially expressed candidate circulating miRNAs between HPH and control groups were validated by Real‐time quantitative PCR based on the case‐control study ,and receiver operating characteristic curve (ROC ) analysis was used to test the performance of four differentially expressed circulating miRNAs in discriminating HPH and control groups .Results Compared with those in the control group ,13 upregulated miRNAs and 10 downregulated miRNAs were identified in hypobaric hypoxia‐induced HPH rats by using miRNA microarray . And differentially expressed miR‐451 , miR‐505 , let‐7d and miR‐214 were validated by using RT‐PCR .ROC analysis showed that the area under the curve of miR‐451 ,miR‐505 and let‐7d was 0 .979 ,0 .938 and 0 .993 in discriminating HPH and control groups ,respectively .Conclusion The aberrant expression of circulating miR‐451 ,miR‐505 and let‐7d in serum may be correlated with the pathogenesis of HPH .

Characteristics of phenylalanine hydroxylase gene mutation in patients with phenylketonuria in Ningxia area / 中华围产医学杂志

Objective To characterize the mutation of phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria(PKU) in Ningxia area,China.Methods Seventy-three children diagnosed with PKU at the Child and Maternal Healthcare Hospital of Ningxia Hui Autonomous Region between January 2010 and June 2013,and 100 non-PKU children randomly chosen from children with normal results in PKU screening were enrolled in the study.Venous blood was collected and the PAH gene sequence was determined by direct DNA sequencing after amplification with the polymerase chain reaction technique.The new gene mutations were defined based on the national and international literature search and databases.The source of the newly discovered mutations was also measured by examining and sequencing the blood samples of their parents.The Chi-square test was used for statistical analysis.Results Among 146 alleles of the 73 PKU children,the detection rate of mutation of PAH gene was 79.5％ (116/146),including 37 types of mutations occurring in 11 exons other than exon 2 and exon 13.The 37 different mutations included 22 missense mutations (59.5％,22/37),six nonsense mutations(16.2％,6/37),six splice site mutations(16.2％,6/37) and three deletion mutations(8.1％,3/37).p.R243Q(17.1％,25/146),EX6-96A ＞ G (6.8％,10/146),p.R241C(6.2％,9/146),p.R413P (5.5％,8/146),p.Rl11X(4.8％,7/146) and IVS4-1G ＞ A(4.8％,7/146) were found to have a higher mutation frequency.Meanwhile,p.R243Q was the most common mutation among Han and Hui ethnic groups with a frequency of 18.8％(12/64) and 15.9％ (13/82),respectively.In contrast,p.R241C showed a significant higher frequency in the Hui group [9.8％(8/82) vs 1.6％(1/64),x2=4.17,P=0.04].Four new mutations of PAH genes,including p.Q304K,p.H107R,p.F392I and p.N223I,were discovered after literature search and comparative studies.Conclusions PAH gene mutations in children with PKU in Ningxia area are unique and are characterized by the diversity and complexity of mutation occurrence in this ethnic region.

Analysis for phenylalanine hydroxylase gene mutations in 35 ethnic Hui children from Ningxia with phenylketonuria / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the type and frequency of phenylalanine hydroxylase gene (PAH) mutations in ethnic Hui patients from Ningxia with phenylketonuria (PKU).</p><p><b>METHODS</b>For 35 PKU children patients and 50 healthy individuals, all exons and promoters of the PAH gene were analyzed with PCR and direct sequencing.</p><p><b>RESULTS</b>Twenty mutations, including 8 missense mutations (40%), 5 nonsense mutations (25%), 4 splice site mutations (20%) and 3 deletion mutants (15%) were discovered. The overall detection rate was 68.57% (48/70). Common mutations have included R243Q (12.86%), R241C (11.43%), EX6-96A to G (5.71%), Y356X (5.71%), R413P(4.29%) and Q232X(4.29%), whilst rarer ones have included S16fsX10 (2.86%), R111X (2.86%) and L430P (2.86%). Among these, S16fsX10, L430P, D222G and IVS11+ 1G to A have not been reported previously. Y414X and S303fsX38 have not been reported in Hui ethnic group. No mutation was detected in the 50 normal controls.</p><p><b>CONCLUSION</b>The types and distribution of PAH gene mutations in ethnic Hui from Ningxia have been different from other areas of China. The mutations also showed a rich diversity.</p>

Mutations of the phenylalanine hydroxylase gene in phenylketonuria patients from Shaanxi / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the feature of phenylalanine hydroxylase (PAH) gene mutations and provide guidance for genetic and prenatal diagnosis of patients with phenylketonuria from Shaanxi.</p><p><b>METHODS</b>For 55 patients whose blood Phe concentration was over 2.0 mg/dL, potential mutations in 13 exons and flanking sequences of the PAH gene were detected by PCR and DNA sequencing.</p><p><b>RESULTS</b>A total of 98 mutations were detected in 110 PAH alleles, with the detection rate being 89.10%. Nine mutations have been identified in exon 7, which accounted for 33.67% of all. Exon 12 (14.29%) and exon 3 (12.24%) have followed. Thirty eight mutations, locating in exon2-exon12 and the flanking sequence, were detected in the 55 PKU patients. p.R243Q (24.49%) was the commonest mutation, whilstp.A47E, p.I65S and p.A259T were first discovered in China. After querying international databases including PAHdb and HGMD, the p.C334X was verified as the novel PAH gene mutation.</p><p><b>CONCLUSION</b>The mutation spectrum of the PAH gene in Shaanxi has been identified. And a novel mutation has been identified. This may facilitate the diagnosis of PKU in the future.</p>

Research on mutations in exon 6 of phenylalanine hydroxylase gene in Ningxia childhood patients / 中华实用儿科临床杂志

Objective To understand the type and frequency of the gene mutation in exon 6 of phenylalanine hydroxylase(PAH) in the children of Ningxia,in order to provide foundation for phenylketonuria(PKU) gene diagnosis and prenatal diagnosis.Methods The exon 6 and flanking introns of 73 cases of classic PKU patients in Ningxia[all confirmed at Ningxia Neonatal Screening Center from Jan.2010 to Jun.2013,and distributed in Ningxia 22 County (city,district),aged from 15 days to 13 years,including 38 male cases,35 female cases,and Hui 39 cases,Han 34 cases] as well as 100 healthy newborn babies(Hui 50 cases;Han 50 cases) were sequentially analyzed by using the approach of PCR direct sequencing.Results There were 6 kinds of mutations detected,including EX6-96A ＞ G(6.85％),Q232X(2.74％),D222G(1.37％),V2301 (1.37％),R176X (0.68％) and N223I (0.68％).Mutation detection rate of exon 6 was 13.70％,and there were 3 mutation types:50.0％ missense mutation (3 types) ;33.3 ％ nonsense mutation (2 types) ;16.7％ cleavage site mutation(1 type).After reviewing the previous studies,the researchers had found out that EX6-96A ＞ G,Q232X and R176X were ever reported in China,and V2301 and D222G had been reported in our country for the first time but N223I was a new kind of PAH gene mutations were not been reported in the world.Conclusions It has defined the gene type and frequency of PAH gene mutations in exon 6 in the children of Ningxia and it will enrich the research of PKU in this area,and provide the basis for the development of gene diagnosis of PKU.

Study on the T cells of T cell receptors BV complementarity determining region 3 lineage polymorphism with peripheral blood in ankylosing spondylitis patients / 中华风湿病学杂志

Objective To study the T cells lineage polymorphism of TCR BV CDR3 in the peripheral blood of ankylosing spondylitis (AS) patients,in order to provide experimental basis for the immunological patho-genesis study of AS.Methods Twenty-six subfamilies of CDR3 T cells of TCR BV in the PBMC of AS patients were amplified by RT-PCR method,then TCR BV CDR3 lineages polymorphism were analyzed by immunization scanning spectrum.Results TCR BV CDR3 scanning spectrum of 20 active AS patients showed abnormal distribution peak,including monoclonal,oligoclonal/oligoclonal trend,skewing peak and irregular abnormal peak.Among them,some subfamilies of 18 patients showed oligoclonal/oligoclonal trend expansion,BV16 and BV18 two subfamilies of one case showed monoclonal expansion.Most spectral type of PBMC TCR BV CDR3 in five normal controls showed Gauss distribution.Conclusion TCR BV CDR3 lineage have significant characteristic polymorphism and spectrum drift characteristics in the peripheral blood of AS patients,which further indicate that T cells has plaied an important role in the immunological pathogenesis of AS.Monoclonal/oligoclonal expansion of T cells may be autoreactive T cells in nature and they may be involved in the pathogenesis of AS.

Analysis of birth defects in Xinjiang multi-ethnic region / 中国组织工程研究

BACKGROUND: Xinjiang is a multi-ethnic region with significant differences in local geographical position, economic development and climatic environment. OBJECTIVE: To analyze the occurrence and development tendency of birth defects, disease categories and disparity among different ethnic groups and regions in Xinjiang.METHODS: A stratified cluster random sampling observation was performed in 13 counties (cities) according to the status of ethnical distribution and local economics of Xinjiang. Quarter Report Sheet on Babies and The defect babies register card were filled as the scheme of Chinese birth defect monitoring, and ICD10 diagnostic code was adopted in birth defect diagnosis. The birth defects rate was calculated from January 2005 to December 2008, and the disease categories and disparity among different ethnic groups and regions in Xinjiang were analyzed. RESULTS AND CONCLUSION: The average incidence rate of birth defect was 9.74‰, which was dramatically descended in 2006 and ascended afterward yearly. The incidence rate of countryside was higher than city, and male more than female. In geography, south of Tianshan Mountain was higher than north and east in birth defect incidence. Among major ethnic groups in Xinjiang, Sibe and Uygur had the highest birth defect incidence rate, followed by Man, Hazakh, and Han. The birth defect incidence of Han, Uygur and Hazakh people showed descend tendency, Hui, Mongolia, and Man people fluctuated, yet Sibe's rate had a change of rise and fall. The first five birth defect entities were neural tube deformity, cleft lips, anencephaly, congenital hydrocephalus and cleft palate combined with cleft lips. The birth defects rates are different from ethnic groups and regions in Xinjiang.

Identification of four novel mutations in the phenylalanine hydroxylase gene in patients with PKU / 中华检验医学杂志

Objective To investigate the distributions of PAH gene mutation and provide guidance for gene diagnosis and prenatal diagnosis of patients with PKU in Xinjiang of China.Methods A total of 15 patients (aged from 2 to 10 years, all with blood Phe concentration over 700 μmol/L) who visited Urumqi general hospital of Lanzhou Command were clinically diagnosed as PKU and were included in this study. PCR followed by DNA sequencing was performed to analyze the promoters, all the 13 exons and their flanking introns of PAH gene in these 15 PKU patients.Results PAH gene of 15 PKU patients was amplified by PCR, and PCR products were subjected to DNA sequencing directly.Four PAH gene mutation types, including 5′- Flanking-626G > A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G>C, were identified in each of four PKU patients.Consequently reverse DNA sequencing showed G>A at -626 site, ACT deletion at -480 position in the promoter of PAH gene, an insertion at 584 site in the coding region and G>C at the border between exon 8 and intron 8 of PAH gene, respectively. After inquirying from PAH website and international PAH database (www.pahdb.mcgill.ca), these four PAH gene mutation types were verified as novel PAH gene mutations. Additionally, four patients carrying either of these four PAH gene mutation aged 3-5 years old were characterized by typical clinical phenotypes including blood Phe levels between 1 572-1 782 μmol/L, mental retardation, yellow hair and mousy odor of hair, skin and urine. Conclusions 5′-Flanking-626G>A, 5′-Flanking-480DelACT, S196fsX4 and IVS8+1G > C are identified as four novel PAH gene mutations to cause PKU directly probably either by disrupting the normal 3-D structure and affecting enzymatic activity of PAH or depressing the transcription and translation of PAH gene.Together, our identification of four novel PAH gene mutations will provide important clues for future gene diagnosis and prenatal diagnosis of PKU.

Potential role of multiple tumor markers chip in preoperative diagnosis of gastric cancer / 国际肿瘤学杂志

Objective To explore the potential value of multiple tumor markers chip( C- 12) in preoperative diagnosis of gastric cancer. Methods The serum levels of 12 rumor markers were measured in 45 gastric cancer patients, 38 benign gastrosis patients and 65 normal controls by use of C-12 in order to find out the most levels of CA199, CEA, CA242, AFP and CA125 in the gastric cancer patients were significantly higher than those of the benign gastrosis patients and normal controls. Moreover, the serum levels of β- HCG and HGH were also significantly higher in gastric cancer group than benign gastric disease group and control group ( P ＜sis of gastric cancer. CEA is the TM with the highest sensitivity, validity and negative predictive value of 57.8% ,81.8% and 77.1% ,respectively whereas CA242 is the TM with the highest specificity and positive CEA + CA125 + CA199 and CEA + CA242 + CA199 + CA125, respectively. The sensitivity, specificity and validity of the best combination of 2 TMs, 3 TMs and 4TMs for gastric cancer were not statistically significantly different from those of C-12 and the best TM ( P ＞ 0.05 ). Conclusion The multiple tumor markers chip ( C-12 ) has a relatively high value in the preoperative diagnosis of gastric cancer. The best combinations of 2 TMs ( CEA + CA125) ,3 TMs ( CEA + CA125 + CA199 ) and 4TMs ( CEA + CA242 + CA199 + CA125 ) for gastric cancer diagnosis could be sufficient to replace the combination of 12 TMs.

Clinical value of multiple tumor marker protein chip detective system in diagnosis and detection of post-operative recurrence of breast cancer / 国际肿瘤学杂志

Objective To evaluate the clinical value of multiple tumor marker protein chip in diagno-sis and detection of postoperative recurrence of breast cancer.Methods The serum levels of 12 tumor makers (CA199,NSE,CEA, CA2A2,Ferritin,β-HCG,AFP,f-PSA,PSA,CA125,CA153 and HGH)were measured in 70 preoperative breast cancer patients, 32 recurrence patients,52 non-recurrence patients and 76 normal con-trois.Results ①The breast cancer group had significantly higher positive rate than that of the controls (P<0.05).The positive rates and serum levels of CA199,CEA,CA242,Ferritin,CAI25 and CA153 in breast cancer patients had those of control significant differences compared with groups (P<0.05).②The recurrence group had significantly higher positive rate than that of non-recurrence group (P<0.05).The positive rates and se-rum levels of CA199, CEA, Ferritin, CA125 and CA153 in the recurrence patients had significant differences compared with those of non-recurrence patients(P<0.05).③The positive rate of recurrence group had signif-icant difference compared with that of breast cancer group(P<0.05).Moreover,The positive rate and serum level of Ferritin in the recurrence patients had significant difference compared with that of breast cancer pa-tients.Conclusion The multiple tumor marker protein chip detective system has valid value of clinical appli-cation in the diagnosis and detection of postoperative recurrence of breast cancer.The combination detection of CA199, CEA, Ferritin ,CA125 and CA153 may be the economical and effective in the diagnosis and detection of postoperative recurrence of breast cancer.

Identification of mutations in phenylalanine hydroxylase gene of Xinjiang minority nationality phenyiketonuria patients / 中华检验医学杂志

Objective To study the mutation characteristics in phenylalanine hydroxylase gene of Xinjiang minority nationality phenylketonuria (PKU) patients and provide a scientific basis for PKU prevention and cure strategy.Methods Mutations in phenylalanine hydroxylase gene were detected by Dolymerase chain reaction-single strand comformation polymorphism (PCR/SSCP) and gene sequencing in 12 minoritv nationality patients.Results Thirteen different mutations,including 8 missense mutations,1 nonsense mutation and 3 splice mutations were found in 24 alleles.The moat common mutations were EX696A＞G and P281 L.which were respectively prevalent in Asia and Europe populations.The common mutations were R243Q,R111X,R176X and F161S.The mutation frequency of R243Q was the highest and R111X was the third highest in Northern China.R176X and F161S were two rare mutations world wide.Especially.F161S was a Chinese-specific mutation because it was for the second time that it was found in China.The mutations detected in this study were first reported in these 3 minority nationality populations,which showed a distinct ethical characteristic.Condusions There is not only a consanguineous relation but also a distinct difference in PAH gene distribution between Xinjiang minority nationality population and yellow race and Latin-American.The results suggest that Xinjiang could probably be a special PAH gene distribution region.

R176X mutant homozygote in phenylketonuria firstly detected in Hui nationality in China: One case report / 中国组织工程研究

BACKGROUND: Phenylketonuria is caused by gene mutation of phenylalanine hydroxylasel (PAH), which is mainly induced by permutation, short segments and insertion of base.OBJECTIVE: To evaluate the gene mutation of phenylalanine hydroxylasel in phenylketonuria in Hui nationality.DESIGN: Open study.SETTING: Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA; Capital Pediatrics Institute.PARTICIPANTS: A boy of Hui nationality in China and aged 3.1 years was selected in this study. The boy had intellect hysteresis in his one year and received medical treatment in his three years, while he was diagnosed as cerebral paralysis. After repeatedly inefficient treatment, he was hospitalized in our hospital on December 13, 2004. Iron sesquichloride in urine was strongly positive and concentration of serum phenylalanine was 1 680 μmol/L; therefore, he was diagnosed as the typical phenylketonuria.METHODS: 5 mL venous blood was selected from the boy and his parents, respectively, and anticoagulated with EDTA-Na2. DNA in gene group was extracted by using typical phenol/chloroform method. In addition, polymerase chain reaction (PCR) primer sequence of extron 7, 6, 11, 3, 12 and 5 of PAH gene was designed based on references. And then, PCR products were detected with 2% agarose gel electrophoresis. 5 μL PCR products were mixed with the same volume of degenerated buffer solution, degenerated at 97 ℃ for 5 minutes, put in iced bath and performed with 80 g/Lnon-degenerated polyacrylamide gel electrophoresis. After that, the products were dealt with sliver staining routinely, and single strand DNA banding patterns were analyzed and recorded. ABI377 automatic sequenator (PE Company) was used to detect PCR sequence and purify PCR product in Shanghai Boya Biotechnology Company.MAIN OUTCOME MEASURES: Iron sesquichloride in urine, concentration of serum phenylalanine and mutant gene types of phenylalanine hydroxylase.RESULTS: Extron 7, 6, 11, 3, 12 and 5 of PAH gene were analyzed in the boy and his parents. The results demonstrated that SSCP electrophoresis in extron 6 was different from that in the normal control group. Site of electrophoresis strip of his father was coincident with that of his mother, but different from that of the boy. Sequencing results indicated that point mutation (cytosine replaced by thymine), which was a R176X mutant heterozygote, occurred at the 526th site of cDNA of phenylalanine hydroxylase gene in his parents; however, two chromosomes of the boy had mutation at the same site, which was R176X mutant homozygote.CONCLUSION: Mutation of R176X homozygote of phenylketonurea is firstly reported in Hui nationality in China.

Relationship between Apolipoprotein E gene and the risk for onset of Alzheimer disease in aged adults in Urumqi / 中国组织工程研究

BACKGROUND: Apolipoprotein E (ApoE) gene polymorphism is associated with the onset of Alzheimer disease (AD), most of the researchers reported that ApoE ε4 allele accounts for familial AD as well as for sporadic AD.OBJECTIVE: This study was designed to validate the relationship between ApoE gene polymorphism and the sporadic AD in Aged Adults in Urumqi, and to evaluate the value of ApoE gene for prediction the risk of sporadic AD.DESIGN: Controlled comparative study based on patients.SETTING: It was conducted at the Institute of Clinical Medicine and the Neurological Department of Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: From January 2001 to January 2003, 60 aged inpatients and outpatients at the Neurological Department of Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA and elderly in the Old People's Home were screened for AD. Of all these participants,28 were males and 32 were females, with an age from 52 to 91, in average of (74.2±19.5) years old, They had 0-16 years education, in average of 4.43 years, 28 were illiterate, 13 were at primary school educational level,12 were at junior middle school educational level, 4 were at high school educational level and 3 were at college educational level. From February to December 2002, 90 genetically unrelated individuals with healthy physical examination findings in Xinjiang area were selected into control group, 59males and 31 females, with an age from 50 to 101 years old, in average of (69.9±25.5) years old, have 0-16 year's education, in average of 7.96years. Of all the controls, 14 were illiterate, 23 were at primary educational level, 25 were at junior middle school educational level, 21 were at high school educational level and 7 were at college educational level. Informed consents were obtained from all the participants.METHODS: 5 Ml blood samples, anticoagulated with ethylene diamine tetraacetic acid (EDTA), were drawn from each participant. Then genome DNA was extracted from peripheral white blood cells using the phenolchloroform method. A fragment containing polymorphism site in exon 4 of ApoE were amplified using the polymerase chain reaction (PCR), were digested with Hha I and were identified using electrophoresis and silver staining. Then, ApoE genotypes and the frequency of ApoE alleles were compared between AD group and control group.MAIN OUTCOME MEASURES: ① ApoE genotypes and the frequency of ApoE alleles were measured in AD group and control group. ② The frequency of ApoE alleles were calculated in participants with different sex,age and educational level in AD group and control group.RESULTS: Sixty patients with AD and 90 healthy individuals participated this investigation. All of them entered the statistical analysis procedure.① The frequency of ε3/ε4 and ε4/ε4 alleles was higher in AD group than in control group (26.67%,11.11%; 3.33%, 1.11%; P ＜ 0.05). The frequency of e2/ε3 in AD group were lower than control group (5.00%,14.00%, P ＜0.05). ② The frequency of ApoE ε4 allele were higher in AD group as compared with control group (17.50%, 7.22%, P ＜ 0.05). The frequency of ApoE ε2 allele were lower in AD group (6.67%, 13.33%, P ＜ 0.05). ③ The frequency of ApoE ε4 allele in females were higher in AD group than in control group (20.97%, 5.00%, P ＜ 0.01). ④ In AD group, patients ≥ 75 years old have a lower frequency of ApoE ε4 allele compared to those less than 75 years (8.57%, 30.00%, P ＜ 0.01). And in individuals less than 75 years old, the frequency of ApoE ε4 allele were higher in AD group than that in control group (30.00%, 7.02%, P ＜ 0.01). ⑤ In illiterate persons and the individuals with only primary school educational level, the frequency of ApoE ε4 allele were higher in AD group than that in control group (10.00%, 0.56%, P ＜ 0.001; 5.00%,1.12%, P ＜ 0.01).CONCLUSION: ① It is proved that ApoE ε4 allele is significantly associated with sporadicAD in Urumqi and ε3/ε4 is the major genotype. ② ApoE ε2 allele has a protective effect on onset of AD. ③ Those individuals，female,less than 75,lower educational level or carrying ApoE ε4 allele take a higher risk of AD.

An Study on the Association of Apolipoprotein E Genetypes with Cerebral infarction and Myocardial infarction in the Urumqi Old Population / 中国医师杂志

Objective To analyse the association of apolipoprotein E genotype with cerebral infarction and myocardial infarction in the old population of Urumqi. Methods The polymerase chain reaction and restriction fragment length polymorphism technique were used to detect the distribution of genotype and gene frequency of ApoE alleles in 56 cases of cerebral infarction(CI), 60 cases of myocardial infarction (MI) and 104 healthy subjects as control. Results The frequency of ApoE ?3/?4 and ?4/?4 genotypes in CI and MI groups was higher than that in control group(P

THE GENE ANALYSIS OF ?-THALASSEMIA MUTATION (IVS-Ⅱ -654, C→T) FOUND IN A FAMILY OF THE HAN NATIONALITY IN XINJIANG / 解放军医学杂志

Gene analysis of the first family with ?-thalassemia in Xinjiang was carried out by polymerase chain reaction (PCR) in combination with dot blot hybridization of allele -specific oligonucleotide (ASO) probes. Seven of the 12 family members were heterozygous for the IVS- Ⅱ-654 (C→T) mutation. The abnormal ? gene of proband was confirmed from the paternal side according to family survey, clinical syndrome and hematological data.

Mutations in exon 5 of the phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria / 解放军医学杂志

Objective To determine the mutations in exon 5 of the phenylalanine hydroxylase(PAH)gene in phenylketonuria(PKU)patients from Xinjiang.Methods The mutations in exon 5 and flanking sequence of PAH gene were detected by SSCP analysis and DNA sequencing.Results Four different mutations,including missence mutation F161S,splice mutation IVS4-1G→A,missence mutation R158Q and nonsence mutation Y166X were identified in 74 chromosomes from 37 PKU patients,with relative frequencies of 4.1%,1.4%,1.4% and 1.4%,respectively.The frequency of mutant alleles in exon 5 is 8.1%.Considering the previous reports and the present study,R158Q was the most prevalent form in PKU patients from European and Latin American countries,IVS4-1G→A was a common mutation inoriental PKU populations.However,F161S and Y166X are two characteristic forms in Chinese.Conclusion Characteristics of PAH gene mutations and their distribution were showed in Chinese PKU population from Xinjiang,where is a hinterland located between China and Europe.The results give a clue that Xinjiang might be an ideal genetic resource repertoire for studying diversity of gene mutations,heterogeneity of PAH gene,human genesis and migration.

Studies on mutations of exon 11 and 12 in phenylalaninase gene of phenylketonuria patients in Xinjiang / 解放军医学杂志

Objective To investigate the point mutation features of exon 11 and 12 in phenylalanine hydroxylase(PAH)gene of the patients with phenylketonuria(PKU)in Xinjiang.Methods PCR/SSCP and gene sequencing were used in present study.Results Five mutations were identified from 74 chromosomes of 37 patients.Among them two mutations were detected from exon 11 including nonsense mutation Y356X and splice site mutation V399V,and three mutations were detected from exon 12 including R413P,R408W and A434D,all which were missense mutation.The frequency of the five mutations were 5.4%,5.4%,4.1%,1.4%,1.4% and 1.4%,respectively.The allelomorphic frequency of exon 11 and 12 were 10.8% and 6.8%,respectively.Among the five mutations,R413P is common in Japan,Y356X and V399V are centered in north China,and R408W is the most often mutation in Europe and America.Conclusion Xinjiang Uygur Autonomous Region is situated on northwest China,contiguous to other countries of central Asia,and is such an area differed from other areas of China,and distributed special PAH gene mutation in PKU patients.