OBJECTIVETo assess the association of variations in chemokines (CCL5, CCL2), chemokine receptor (CCR5 and CCR2) genes with susceptibility to myocardial infarction (MI) through a case-control study.

METHODSGenotypes of patients with MI (n = 634) were compared with those of controls (n = 601). Genetic polymorphisms of CCL5 rs2107538 (-403G > A), CCL2 rs1024611 (-2518A > G), CCR5 rs333 ( δ 32 ins or del) and CCR2 rs1799864 (190G > A) of 1235 individuals were determined with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Particular genotypes were confirmed with DNA sequencing.

RESULTSNo subject was found to carry the CCR5 - δ 32 allele. No association was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For CCL5 rs2107538 polymorphism, the A allele has occurred at a higher frequency in MI patients than controls, and its AA genotype has been associated with a significantly increased risk of MI independent of conventional risk factors (OR = 3.346, 95%CI = 1.938-5.775, P < 0.01, AA vs. GG). Further analysis indicated that MI patients had significantly more A-403 - A-2518 haplotype (CCL5 -403G > A and CCL2 -2518A > G, 21.8% vs. 26.6%, OR = 1.229, 95%CI = 1.012-1.493, P = 0.038) and AA or AA genotype (CCL5 -403G > A - CCL2 -2518A > G, 5.0% vs. 12.1%, OR = 3.245, 95%CI = 1.780-5.914, P < 0.01).

CONCLUSIONAlthough our data dose not support an association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms and MI, genetic variation in CCL5 gene may still be a useful marker for assessing susceptibility to MI in ethnic Han Chinese population.

Aged ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Case-Control Studies ; Chemokine CCL2 ; chemistry ; Chemokine CCL5 ; genetics ; China ; epidemiology ; ethnology ; Female ; Genetic Association Studies ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Myocardial Infarction ; epidemiology ; ethnology ; genetics ; Polymorphism, Single Nucleotide ; Receptors, CCR2 ; genetics ; Receptors, CCR5 ; genetics ; Risk Factors

OBJECTIVETo analyze TRAPPC2 gene mutation in a family with X-linked spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal diagnosis.

METHODSAll of 4 exons of the TRAPPC2 gene and their flanking sequences in the proband and her father were analyzed with polymerase chain reaction and direct DNA sequencing. Genomic DNA of the probands' fetus was extracted from amniotic fluid sampled at 18th gestational week. Gender of the fetus was determined by the presence of SRY gene. The sequence of fetal TRAPPC2 gene was also analyzed.

RESULTSA c.209G>A mutation was identified in exon 4 of the TRAPPC2 gene in the proband and her father. The fetus of was determined to be a male and also have carried the c.209G>A mutation.

CONCLUSIONA c.209G>A mutation of TRAPPC2 exon 4 probably underlies the clinical manifestations in this family. The proband is a carrier, and her fetus is a male carrying the same mutation. Prenatal diagnosis is an effective method for the prevention of the disease.

Base Sequence ; Female ; Genetic Counseling ; Genetic Diseases, X-Linked ; diagnosis ; embryology ; genetics ; Humans ; Molecular Sequence Data ; Osteochondrodysplasias ; genetics ; Point Mutation ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population.

METHODSA total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis.

RESULTSThe repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481).

CONCLUSIONOur data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.

Adolescent ; Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Humans ; Male ; Minisatellite Repeats ; Pedigree ; Polymorphism, Genetic ; Tourette Syndrome ; ethnology ; genetics ; Young Adult

OBJECTIVETo explore the clinical feature, therapeutic effect and prognosis of isolated methylmalonic acidemia.

METHODSThe clinical characteristics, laboratory findings, treatment and outcome of 40 patients were retrospectively analyzed. The main treatment was a low-protein diet supplemented with L-carnitine and special milk free of leucine, valine, threonine and methionine. Vitamin B12 was also given to cobalamin responders. The patients were followed up every 1-3 months.

RESULTSMutations in the MUT gene were identified in 30 of 33 patients who had accepted DNA testing. Thirty cases were treated and followed up regularly for from 1 month to 8 years. Eight cases had died, 8 had developed normal intelligence, among whom 4 from newborn screening were asymptomatic. Psychomotor developmental delay and mental retardation were present in 14 cases. The propionylcarnitine level, ratio of propionylcarnitine/acetylcarnitine in blood, methylmalonic acid and methylcitric acid levels in urine have decreased significantly, with the median values reduced respectively from 24.15 (7.92-81.02) μmol/L, 1.08 (0.38-6.01), 705.34 (113.79-3078.60) and 7.71 (0.52-128.21) to 10.50 (3.00-30.92) μmol/L, 0.63 (0.25-2.89), 166.23 (22.40-3322.21) and 3.96 (0.94-119.13) (P < 0.05).

CONCLUSIONThe prognosis of isolated methylmalonic acidemia may be predicted with the enzymatic subgroup, age at onset and cobalamin responsiveness. Outcome is unfavorable in neonatal patients and those who were non-responsive to cobalamin.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; diet therapy ; enzymology ; metabolism ; Carnitine ; metabolism ; Child ; Child, Preschool ; Diet, Protein-Restricted ; utilization ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Methylmalonyl-CoA Mutase ; genetics ; Retrospective Studies

OBJECTIVETo investigate clinical and imaging features of a patient with adult-onset Krabbe disease and to detect the underlying genetic mutations.

METHODSClinical and cranial MRI features of the patient were analyzed. Pathogenesis, clinical manifestation, cranial MRI features and diagnostic criteria for the disease were discussed.

RESULTSThe patient had presented asymmetric limb weakness and difficulty in walking. Electromyography suggested peripheral nerve demyelination. Cranial MRI showed increased signal intensity in white matter with involvement of the corticospinal tracts. Screening of GALC gene mutation has found the patient to be heterozygous for T1685C (Ile562Thr) and homozygous for A1921G (Thr641Ala), both of which were considered to be polymorphisms. In addition, he was heterozygous for G136T (Asp46Tyr), which had not been described previously.

CONCLUSIONClinical manifestations of adult-onset Krabbe disease may be atypical. Cranial MRI and galactocerebroside activity assay should be carried out for patients featuring chronic progressive corticospinal tract injury. An Asp46Tyr mutation probably underlies the disease in the current case.

Adult ; Base Sequence ; Brain ; diagnostic imaging ; Female ; Humans ; Leukodystrophy, Globoid Cell ; diagnosis ; diagnostic imaging ; genetics ; Magnetic Resonance Imaging ; Molecular Sequence Data ; Point Mutation ; Radiography

OBJECTIVETo screen potential mutations of PHEX gene in a family featuring hypophosphatemic rickets in order to confirm the molecular diagnosis and pathogenetic mechanism.

METHODSGenomic DNA was extracted from peripheral venous blood samples. DNA sequence of PHEX gene was derived from UCSC database, and primers for its coding region were designed with Primer premier 5.0. Potential mutations were detected with PCR amplification and DNA sequence analysis.

RESUTLSA mutation was identified in intron 6 of the PHEX gene in the proband and his mother.

CONCLUSIONThe c.732+1G>T mutation underlies the hypophosphatemic rickets in this family.

Adult ; Base Sequence ; Child ; Female ; Humans ; Hypophosphatasia ; enzymology ; genetics ; Introns ; Male ; Molecular Sequence Data ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Pedigree

OBJECTIVETo detect potential mutation in a Chinese family where two individuals were affected with hereditary congenital aniridia.

METHODSPeripheral blood samples were taken for genomic DNA extraction. All of the 15 exons of PAX6 gene were amplified with PCR. The product were purified with gel electrophoresis and sequenced.

RESULTSIn both patients, a novel deletion mutation (c.957-958delCA) in exon 13 of the PAX6 gene was identified, which has produced a terminator codon. The same mutation was not found in healthy controls.

CONCLUSIONA c.957-958delCA mutation of PAX6 gene is probably the cause of aniridia in this Chinese family.

Adult ; Aniridia ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Exons ; Eye Proteins ; genetics ; Female ; Homeodomain Proteins ; genetics ; Humans ; Male ; Molecular Sequence Data ; PAX6 Transcription Factor ; Paired Box Transcription Factors ; genetics ; Pedigree ; Repressor Proteins ; genetics ; Sequence Deletion

OBJECTIVETo report on 5 patients with maternal 3-methylcrotonyl coenzyme A carboxylase deficiency (MCCD) and to confirm the clinical diagnosis through mutation analysis.

METHODSFive neonates with higher blood 3-hydroxy isovalerylcarnitine (C5-OH) concentration detected upon newborn screening with tandem mass spectrometry and their mothers were recruited. Urinary organic acids were analyzed with gas chromatography mass spectrometry. Gene mutation and protein function analysis were performed by PCR direct sequencing and PolyPhen-2 software.

RESULTSHigher blood C5-OH concentrations (5.11-21.77 μmol/L) and abnormal 3-hydroxy isovalerate and 3-methylcrotonyl glycine in urine were detected in the five asymptomatic mothers, who were diagnosed as benign MCCD. Higher C5-OH concentration was also detected in their neonates by tandem mass spectrometry, which had gradually decreased to normal levels in three neonates. Four new variations, i.e., c.ins1680A(25%), c.203C > T (p.A68V), c.572T > C (p.L191P) and c.639+5G > T were detected in the MCCC1 gene, in addition with 2 mutations [c.1406G > T (p.R469L, novel variation) and c.592C > T (p.Q198X)]. The novel variations were predicted to have affected protein structure and function.

CONCLUSIONFor neonates with higher C5-OH concentration detected upon neonatal screening, their mothers should be also tested to rule out MCCD. Mutations in MCCC1 gene are quite common.

Adult ; Amino Acid Sequence ; Base Sequence ; Carbon-Carbon Ligases ; blood ; deficiency ; genetics ; Carnitine ; analogs & derivatives ; blood ; DNA Mutational Analysis ; Female ; Genomic Imprinting ; Humans ; Infant, Newborn ; Male ; Molecular Sequence Data ; Mutation ; Neonatal Screening ; Sex Factors ; Tandem Mass Spectrometry ; Urea Cycle Disorders, Inborn ; blood ; diagnosis ; enzymology ; genetics

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disease initially reported by Bardet and Biedl in the 1920s. BBS is a pleiotropic and genetically heterogeneous disorder characterized by retinopathy, obesity, polydactyly, renal malformations and functional abnormalities, learning disabilities and hypogenitalism. BBS patients are also prone to diabetes mellitus, hypertension and congenital heart disease. To date, 16 BBS genes (BBS1-BBS16) have been identified. However, the molecular etiology of BBS is not yet entirely clear. In this article, we have reviewed recent research on BBS and discussed its implications for understanding of ciliopathology.
Animals ; Bardet-Biedl Syndrome ; complications ; genetics ; metabolism ; Biomedical Research ; Humans ; Obesity ; etiology

Sustained activation of sympathetic nervous system in response to stimulation of a wide variety of stress factors is an independent risk factor for the development of essential hypertension. Adrenal hormone biosynthesis pathway as an important part of the sympathetic nervous system consists of hormones, neurotransmitters, receptors, and a variety of synthases and invertases. In this article, we have systematically reviewed research progresses made in elucidating the interactions between genes of the adrenal hormone biosynthesis pathway and stress factors in the pathogenesis of essential hypertension.
Animals ; Hormones ; metabolism ; Humans ; Hypertension ; genetics ; metabolism ; pathology ; Sympathetic Nervous System ; metabolism ; pathology