Mutation analysis of the PAH gene in children with phenylketonuria from the Qinghai area of China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the mutation characteristics of the phenylalanine hydroxylase (PAH) gene in children with phenylketonuria (PKU) from the Qinghai area of China, in order to provide basic information for genetic counseling and prenatal diagnosis.</p><p><b>METHODS</b>Mutations of the PAH gene were detected in the promoter and exons 1-13 and their flanking intronic sequences of PAH gene by PCR and DNA sequencing in 49 children with PKU and their parents from the Qinghai area of China.</p><p><b>RESULTS</b>A total of 30 different mutations were detected in 80 out of 98 mutant alleles (82%), including 19 missense (63%), 5 nonsense (17%), 3 splice-site (10%) and 3 deletions (10%). Most mutations were detected in exons 3, 6, 7, 11 and intron 4 of PAH gene. The most frequent mutations were p.R243Q (19%), IVS4-1G>A (9%), p.Y356X (7%) and p.EX6-96A>G(5%). Two novel mutations p.N93fsX5 (c.279-282delCATC) and p.G171E (c.512G>A) were found. p.H64fsX9(c.190delC) was documented for the second time in Chinese PAH gene. The mutation spectrum of the gene PAH in the Qinghai population was similar to that in other populations in North China while significantly different from that in the populations from some provinces in southern China, Japan and Europe.</p><p><b>CONCLUSIONS</b>The mutations of PAH gene in the Qinghai area of China demonstrate a unique diversity, complexity and specificity.</p>

Analysis of mutations in exon 7 of phenylalanine hydroxylase gene among children with phenylketonuria in Ningxia, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the type and frequency of mutations in exon 7 of phenylalanine hydroxylase (PAH) gene among children with phenylketonuria (PKU) in Ningxia, China and to provide a basis for the genetic diagnosis and prenatal diagnosis of PKU in this region.</p><p><b>METHODS</b>Direct sequencing of PCR product was performed to analyze the sequences of exon 7 and its flanking introns of 146 PAH alleles in 73 children with typical PKU (39 cases of Hui nationality and 34 cases of Han nationality) in Ningxia.</p><p><b>RESULTS</b>Six mutations were detected, including R243Q (14.4%), R241C (6.8%), IVS7+2T→A (2.7%), L255S (0.7%), G247V (0.7%), and G247R (0.7%). The overall frequency of mutations (missense mutation and splice site mutation) in exon 7 was 26.0% (38/146). The detection rate of R241C mutation was significantly higher in children of Hui nationality than in children of Han nationality(10% vs 3%; P<0.05).</p><p><b>CONCLUSIONS</b>In Ningxia, R243Q mutation in exon 7 of PAH gene is most common in children with PKU, followed by R241C. The frequency of R241C mutation in exon 7 of PAH gene varies between children with PKU of Hui and Han nationality.</p>

Sperm DNA damage in young men working on the plateau / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate whether long working in the high-altitude area can damage sperm DNA in men.</p><p><b>METHODS</b>We enlisted 51 service men stationed on the plateau in an observation group and another 53 living in the low-altitude area in a control group. We detected and compared the damages to sperm DNA in the semen samples from the two groups using single cell gel electrophoresis and the sperm chromatin dispersion test.</p><p><b>RESULTS</b>The percentages of total, G1, G2 and G3 comet cells and abnormal sperm of the observation group were (5.56 +/- 3.98)%, (3.72 +/- 1.85)%, (1.57 +/- 1.07)%, (0.27 +/- 0.34)% and (16.59 +/- 12.07)%, respectively, before stationed on the plateau, but significantly increased at 6 months of plateau life ([11.15 +/- 8.59]%, [5.97 +/- 3.26]%, [3.83 +/- 2.13%, [1.35 +/- 1.53]% and [22.03 +/- 15.33]%, P<0.05). The percentages of G2 comet cells and abnormal sperm were decreased to (3.32 +/- 1.83)% and (20.54 +/- 15.52)% at 12 months, but still significantly higher than the baseline (P<0.05).</p><p><b>CONCLUSION</b>Long working on the plateau may damage sperm DNA, but its influence on male fertility deserves further investigation. Therefore, it is important to reinforce reproductive health protection for males working on the plateau.</p>

Characteristics of the PAH gene mutation in Chinese patients with phenylketonuria in Xinjiang / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the characteristics of the PAH gene mutation in patients with phenylketonuria (PKU) in Xinjiang area.</p><p><b>METHODS</b>The mutations in exons 3, 5, 6, 7, 11 and 12 and the flanking intronic sequence of the PAH gene were detected by PCR/SSCP analysis and direct DNA sequencing in 46 PKU patients.</p><p><b>RESULTS</b>Twenty different mutations were found in 68/92 alleles (73.9%). The prevalent mutations of R243Q, EX6 96A>G, R111X, Y356X and V399V were similar to that of Northern China populations. The mutations F161S, L255S, P281L, and R413P were significantly different from that in other Chinese populations. It was the second time that E280G and A434D mutations were reported in the world, that L255S, P281L, R261Q, and I65T mutations were found in China. Thirteen different mutations were first found in Chinese Uygur, which showed a distinct ethnic characteristics.</p><p><b>CONCLUSION</b>The study showed not only a distinct and conservative, but also a crossed and syncretic genetic characteristics in Xinjiang Uygur population. The results suggest that Xinjiang could be an ideal genetic resource repertoire for studying diversity of gene mutations, heterogeneity of PAH gene, human origins and migration.</p>

Semen analysis of sterile patients among occupational computermen / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore temn possible correlation between the computer occupational semen quality.</p><p><b>METHODS</b>We included in this study 224 sterile males (118 computermen and 106 non-computermen) treated in our clinic of male sterility and 125 normal fertile men as controls, and analyzed such parameters as semen liquefaction time and sperm density, vitality and motility according to the WHO standard.</p><p><b>RESULTS</b>Compared with the normal controls, there was a significant decrease in the semen volume and sperm density, vitality and motility (P < 0.05-0.01) and a marked increase in liquefaction time in the infertile computermen and non-computermen (P < 0.01). The semen volume and sperm vitality and motility were significantly lower in the infertile computermen than in the infertile non-eomputermen (P < 0.05). The three parameters were also significantly decreased in the 0-5, 6-10 and > 10 h/d computer use groups. Similarly, significantly lower sperm density, vitality and motility were observed in the > 10 hid group than in the 0-5 and 6-10 h/d groups (P < 0.05-0.01), but with no statistical difference between the latter two (P > 0.05).</p><p><b>CONCLUSION</b>Computer occupation is associated with abnormal semen quality, and long-term computer use ( > 10 h/d) may be one of the factors of male infertility.</p>

The mutant spectrum of phenylalanine hydroxylase gene in Northern Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To understand the mutant spectrum of phenylalanine hydroxylase (PAH) gene in Northern Chinese.</p><p><b>METHODS</b>All the exons and flaking introns of PAH gene were detected by PCR-single strand conformation polymorphism (PCR/SSCP) and sequencing in 230 patients with phenylketonuria (PKU).</p><p><b>RESULTS</b>(1) A total of 75 different mutations were detected in 435 out of 460 mutant alleles (94.6%). Among them 3 mutations (S251-R252>SfsX89, Y387D and A389G) have not been reported previously. The mutations, R243Q, EX6-96A>G, R111X, R413P and Y356X, were the prevalent mutations with relative frequencies of 21.7%, 10.2%, 8.3%, 6.5%, and 6.1% respectively, followed by V399V(4.1%), IVS4-1G>A (3.5%), IVS7+2T>A (2.2%) and R241C(2.2%). Most mutations were detected in exons 3, 5, 6, 7, 11 and 12 and flaking introns of PAH gene. (2) Ten polymorphism sites were detected in the study. Four sites, IVS3-22C>T, IVS10+97G>A, Q232Q and V245V, had high relative frequencies of 56.7%, 75.9%, 89.0% and 81.9% respectively. It would suggest that the race diversity exists in PAH cDNA sequence.</p><p><b>CONCLUSION</b>The mutation spectrum of PAH gene in Northern Chinese is similar to other Asian populations but significantly different from European populations.</p>

Comparison of sperm parameters between male adults at different altitudes / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the influence of long-term anoxic exposure on the sperm function of male adults at different altitudes.</p><p><b>METHODS</b>A total of 28 male adults that had stayed at the altitude of 5 340 m for 1-3 years were included as a high-altitude group (HAG), 34 at the mean altitude of 3 800 m for 2-5 years as a middle-altitude group (MAG) and 31 permanently at the altitude of 1 300 m as controls. Semen specimens were collected and the real-time semen analysis was performed by using computer-assisted semen analysis (CASA) system.</p><p><b>RESULTS</b>The sperm density, VCL, VSL, VAP and LIN in the HAG were (51.12 +/- 14.61) x 10(6)/ ml, (48.17 +/- 13. 52) microm/s, (32.64 +/- 6.70) microm/s, (41.21 +/- 9.32) microm/s and 52.24 +/- 8.14, respectively, significantly lower than those of the control (P < 0.01 or P < 0.05). Compared with the control group, there was a progressive decrease in sperm concentration, sperm motility rate, VSL, VCL, LIN, VAP and ALH in the MAG.</p><p><b>CONCLUSION</b>The higher the altitude, the more obvious was the negative effect of anoxic exposure on the sperm function of male adults.</p>

Mutations in exon 7 of the PAH gene in Chinese phenylketonuria patients in Xinjiang / 中华检验医学杂志

Objective To investigate the mutation characteristics in exon 7 of the PAH gene in phenylketonuria(PKU) patients in Xinjiang.Methods The mutations in exon 7 of PAH gene were detected by PCR/SSCP in 37 PKU patients.Results Five missense mutations including R243Q,L255S,E280G, E280K and P281L were identified in 74 chromosomes from 37 PKU patients,with relative frequencies of 18.9%,4.1%,1.4%,1.4% and 1.4% respectively.The frequency of mutant alleles in exon 7 was 27%. Among the five mutations,it was the second time the E280G mutation was reported in the world.In China,it was the second time the L255S,E280K and P281 L mutations were found.P281L and R243Q mutations were first found in 2 of Chinese Uygur.Considering the previous reports and the present study,R243Q was the most prevalent form in Asian PKU populations.P281L and E280K were two common mutations in PKU patients from European countries.However,E280G and L255S were two characteristic forms in Chinese. Condusions Characteristics of PAH gene mutations are shown in Chinese PKU population from Xinjiang, which is a special distribution belt that located between China and Europe.The results give a clue that Xinjiang could probably be an ideal genetic resource repertoire for studying diversity of gene mutations, heterogeneity of PAH gene,human genesis and migration.