Objective To identify mutations site and clinical characteristics of a familial hypercholesterolemia(FH) proband diagnosed clinically through DNA sequencing and family analysis in the proband and his family members of 3 generations.Methods Blood samples and clinical data of the kindred of total 29 from 3 generations members were collected.Proband had a physical examination electrocar-diogrom and vascular ultrasound.The proband and his family members took routine clinical exams,and genomic DNA was isolated.The promoter region and the 18 exons of low density liporotein receptor(LDLR) gene were screened by Touch down polymerase chain reaction -single strand conformation polymorphism(PCR-SSCP) and DNA sequencing.The result of sequencing were matched gene sequence published in the BLAST database.Results 1.Increased intima-media thickness and plaque were detected in the common carotid artery,right subclavian artery of the proband.Aortic valve regurgitation was found by echocardiography.2.No mutation R3500Q of ApoB100 was observed.3.Two heterozygous mutations in exon 10 and 13 of LDLR gene (W462X and A606T) were identified.The proband and 5 members of paternal relatives showed W462X heterozygosis mutation in exon 10 of LDLR gene which introduced the change from tryptophone to a new stop codon.The proband's mother and grandmother harboured A606T heterozygous mutation in exon 13 of LDLR gene due to a single base pair substitution of G for A in the codon for residue 1 879.Conclusions Disease causing mutations of proband are W462X and A606T compound heterozygosis mutation in exon 10 and 13 of LDLR gene inherited from mother and father.Proband shows homozyous phenotype though the genotype analysis indicates heterozygous mutations.

With the rapid development of medical genetics,online Medelian inheritance in man (OMIM) manifests a more and more important role in medical genetics teaching.Using the educational form combining ‘ classroom teaching,review writing and seminar’,‘ Query and use of OMIM ’was introduced into the education of medical genetics.Reality practice revealed that this educational practice maintained advanced and timely status of knowledge and deeply activated self-studying and independent thinking ability of students.

Objective To explore the prevention effect of points massage on the cerebral hemorrhage patients with constipation.Methods Totals of 160 cases of acute cerebral hemorrhage within 7 d were randomly divided into observation group (n =80) and control group (n =80).All cases received the routine care,and patients in observation group received the points massage.Then,the incidence of constipation of two groups,the blood pressure and heart rate of observation group before and after intervention were observed.Results The incidence of constipation after cerebral hemorrhage in observation group was 16.25％ and that of the control group was 43.75％,and the difference was statistically significant (x2 =14.40,P ＜ 0.01).Before and after intervention,the heart rate and blood pressure in observation group had no significant difference (t =0.21,-0.28,0.44 ;P ＞ 0.05).Conclusions Points massage is benefit to patients for preventing constipation after cerebral hemorrhage.

Objective To explore the molecular basis of familial hypercholesteraemia(FH)by analyzing the phenotype and genotype relationship through identify the low density liporotein receptor(LDL-r)gene mutation in a FH kindred.Methods A male patient of 15 years old was selected to examine the electrocardiogram,lipid.Color Doppler was used to examine heart and great vessels.The promoter region and the 18 exons of the LDL-r gene were screened by touch-down polymerase chain reaction(PCR)and DNA sequencing.Results The caro-tid intima-media thickness(IMT)was increased to 0.23 cm,while coronary flow velocity reserve(CFVR)was decreased to 1.57,and mode-rate mitral regurgitation was found in the proband.The genetic alteration G→A change at 1 448 of exon 10 causing premature stop codon(W462X).The same heterozygous nonsense mutation was also found in his father.The mutation had been reported in other Chinese patients.In vitro experiments showed that W462X mutation leads to low LDL binding and internalization ability.Conclusions The homozygous mutation(W462X)in exon 10 of the LDL-r gene were identified in the clinically heterozygous FH proband.The W462X mutation is the underl-ying cause of hypercholesterolaemia and clinical AS manifestations.W462X is recurrent mutation among Chinese FH patients.It might be a hot spot mutation in LDL-r in Chinese FH.J Appl Clin Pediatr,2009,24(1):18-20

OBJECTIVETo report a case of myelodysplastic syndrome(MDS) with t(1;18)(p31;p11).

METHODSChromosome specimens were prepared by short-term culture of bone marrow cells. Karyotype analysis was made by R banding technique. Chromosome painting was performed using whole chromosome probes 1 and 18.

RESULTSConventional karyotype analysis revealed t(1;18)(p31;p11) in this patient. Chromosome painting analysis confirmed this result.

CONCLUSIONThe translocation of (1;18) was an unusual recurrent chromosome change and was reported on MDS for the first time.

Adult ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 18 ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Myelodysplastic Syndromes ; genetics ; Translocation, Genetic ; genetics

OBJECTIVETo determine the value of fluorescence in situ hybridization (FISH) to the diagnosis of chromosome abnormality in genetic diseases and prenatal diagnosis.

METHODSFISH was performed using appropriate probes, including alpha-satellite DNA probe, chromosome sequence specific probe and whole chromosome painting probe, to examine the blood samples from 36 patients who were suspected of having chromosome abnormality by conventional cytogenetics, and to examine the amniocytes from 45 pregnant women who were in need of prenatal diagnosis.

RESULTSAmong 36 patients, the following karyotypes 45, X; 45, X/46, XX; 45, X/46, Xr(X); 46, X, i(Xq); 47, XXY; 46, XX, t(4;7); 47, XYY; 47, XXX; 47, XXY, inv(7); 46, XY, inv(7); 47, XX, +21 were detected by FISH. Of the fetuses of the 45 pregnant women, two fetuses with chromosomal abnormalities were diagnosed by FISH; the karyotypes were 47, XX, +18 and 46, XY, der(15) t(Y;15) respectively.

CONCLUSIONFISH can precisely and rapidly detect the chromosome abnormalities. It is a complement to the conventional cytogenetics and can be widely used in the diagnosis of genetic diseases and prenatal diagnosis.

Adult ; Amniocentesis ; Chromosome Aberrations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Male ; Prenatal Diagnosis ; Sex Chromosome Aberrations ; Turner Syndrome ; diagnosis

OBJECTIVETo evaluate the association of gr/gr deletion in the AZFc region of Y chromosome with idiopathic male infertility using Meta-analysis.

METHODSAll relevant case-control studies addressing the relationship between gr/gr deletion and idiopathic male infertility were identified from PubMed, VIP and CNKI (from January 2003 to August 2010). Statistical analyses were performed with the RevMan4. 2 software.

RESULTSTwenty eligible articles were selected in this study, including 5 246 cases of idiopathic infertility and 4 380 controls. The integrated data from the 20 studies revealed a significantly higher frequency of gr/gr deletion in the patients than in the controls, with an odds ratio (OR) of 1.63 (95% CI: 1.23 -2.44) (P = 0.002). However, when the Meta-analysis was limited to 16 studies with stricter case and control selection criteria, the overall OR increased to 1.84 (95% CI: 1.47 - 2.29) (P < 0.000 01). Thirteen studies showed that oligozoospermia patients had a significantly higher frequency of gr/gr deletion than controls (OR = 2.12, 95% CI: 1.61 - 2.80) (P < 0.000 01). Eight studies showed a significant association between the gr/gr deletion subtype without DAZ1/DAZ2 gene copies and spermatogenic impairment (OR = 1.83, 95% CI: 1.31 - 2.55) (P = 0.000 4), but no statistically significant differences were found in the frequency distribution of the gr/gr deletion subtype missing DAZ3/DAZ4 gene copies between the patients and controls (OR = 1.43, 95% CI: 0.97 -2.11) (P = 0.07).

CONCLUSIONThe present data suggest that gr/gr deletion may be one of the risk factors of male infertility.

Chromosome Deletion ; Chromosomes, Human, Y ; Humans ; Infertility, Male ; genetics ; Male

To explore the value of detection of PML/RARalpha gene rearrangement on bone marrow smears (BMS) by dual-color fluorescence in situ hybridization (D-FISH) for the diagnosis of acute promyelocytic leukemia (APL), the locus-specific probes for PML and RARalpha genes labeled directly and respectively by Spectrum Green and Spectrum Orange and the D-FISH technique were used to detect the PML/RARalpha gene rearrangement on BMS in 27 suspected APL patients. The results were compared with that of conventional cytogentics (CCG) and reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that out of 18 newly diagnosed patients 14 were found having t(15;17) translocation by CCG and PML/RARalpha gene rearrangement were confirmed by BMS-D-FISH and RT-PCR. Thus, their APL diagnosis was determined; out of 4 patients in whom t(15;17) translocation was not detected by CCG, one had positive BMS-D-FISH and RT-PCR results, thus, this case was considered as having a cryptic t(15;17) translocation, three had negative BMS-D-FISH and RT-PCR results, thus, they were diagnosed as having acute myeloid leukemia rather than APL. In 9 cases with remission, one case with partial remission was found having t(15;17) translocation by CCG, and he had positive BMS-D-FISH and RT-PCR results, the other 8 patients (6 cases with normal karyotype and 2 cases without CCG examination) displayed different BMS-D-FISH and RT-PCR results: negative in 6 cases, but positive in 2 cases. The 2 cases were believed that they survived with minimal residual disease (MRD). It is concluded that BMS-D-FISH is a sensitive and reliable method for the detection of PML/RARalpha rearrangement. It is helpful for diagnosing APL and monitoring its MRD, and especially fit to those patients presenting a cryptic translocation or with failed cytogenetics, lacking suitable material for RT-PCR, as well as needing retrospective study.
Adolescent ; Adult ; Bone Marrow Cells ; metabolism ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Leukemia, Promyelocytic, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Receptors, Retinoic Acid ; genetics ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.
Alleles ; Allopurinol ; adverse effects ; Anti-HIV Agents ; adverse effects ; Anticonvulsants ; adverse effects ; Carbamazepine ; adverse effects ; Dideoxynucleosides ; adverse effects ; Drug Hypersensitivity Syndrome ; etiology ; immunology ; Drug-Related Side Effects and Adverse Reactions ; genetics ; immunology ; Enzyme Inhibitors ; adverse effects ; Genome-Wide Association Study ; HLA Antigens ; genetics ; HLA-B Antigens ; immunology ; HLA-B15 Antigen ; immunology ; Humans ; Stevens-Johnson Syndrome ; etiology ; immunology

OBJECTIVETo determine the frequency of the derivative 9 [der(9)] deletion among chronic myeloid leukemia (CML) patients with classic and variant Ph translocations, and assess the correlation between this deletion and clinical prognosis.

METHODSCytogenetic analysis of bone marrow cells was performed by direct method and/or 24 h culture method. RHG banding was used for karyotype analysis. Dual-color and dual-fusion DNA probe was used to perform FISH for investigating the deletion of der(9) in Ph+ CML patients.

RESULTSCytogenetics studies showed typical Ph translocation in 76/105 and variant Ph translocation in 29/105 cases. Interphase-FISH studies showed deletion of der(9) in 12 (15.8%) of 76 patients with classic Ph translocation and in 4 (13.7%) of 29 patients with variant translocation. The frequency of deletion was similar in classic and variant translocations (P > 0.05). When the deletion was seen in the patient, it was present in all the Ph+ metaphases and nuclei. In 3 patients there were mixed cell populations with either 5'-abl or 3'-bcr deletion and all the 3 patients had both 5'-abl and 3'-bcr deletion. The median survival time of patients with deletion was significantly shorter than those without deletion (34 months vs 76 months; P < 0.05).

CONCLUSIONDeletion of der(9) is seen in about 1/6 of Ph+ CML patients in our study on Chinese CML patients, Ph+ CML patients with the deletion have shorter median survival time than those without it, indicating that it is a poor prognostic index.

Adolescent ; Adult ; Aged ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; mortality ; Male ; Middle Aged ; Philadelphia Chromosome ; Prognosis ; Survival Rate ; Translocation, Genetic ; Young Adult