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Objective X-linked adrenoleukodystrophy (X-ALD) is a genetically determined disorder that is characterized by demyelination of central nervous system,and impaired adrenal cortex and abnormal accumulation of very long chain fatty acids in body fluid and tissue.The clinical manifestation,biochemical change,and magnetic resonance imaging were analyzed.Methods Clinical data of 11 cases with X-ALD were summarized and analyzed,including symptoms,signs,and inspection result.Relevant literature was reviewed.Results All cases were males,whose average onset age was (7.2 ± 4.7) year-old.It was (2.4 ± 1.9) years that the mean interval appears from onset to diagnosis.Six cases were with onset of adrenal insufficiency (AI),remaining 5 onset neural symptoms,where plasma very-long-chain fatty acids (VLCFA) was tested in 6 patients,all with abnormally high levels and brain magnetic resonance imaging(MRI) showed demyelination of cerebral white matter in 9 ones.Conclusions ALD is a X-linked genetically determined disorder that mainly affects the nervous system and adrenal gland.Plasma VLCFA test,ALD gene test,and cerebral MRI are reliable diagnostic methods.Early diagnosis and appropriate therapy would improve survival and neurological outcomes.
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Objective To initially map the gene responsible for autosomal dominant familial IgA nephropathy of a Chinese family by exclusive the five loci that had been reported with linkage analysis.Methods The genetic pattern of the familial IgA nephropathy was identified and the genomic DNA was extracted from the blood samples collected from the family members.Short tandem repeat (STR) inside the loci that had been reported was selected,such as 2q36,3p23-24,4q26-31,6q22-23,17q12-22,and the data with two-point linkage analysis were performed.Results Autosomal dominant inheritance pattern was demonstrated in phenotypes of the family and there was no linkage relationship in the above five loci of chromosomes because the maximum two-point LOD score was 0.39 at D17S1868.Conclusion Following exclusion of the loci which had been reported,there are other new pathopoiesis loci of FIgAN and it reveals that FIgAN has the genetic heterogeneity according to initial result at the same time.
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Objective To explore the prenatal genetic diagnosis for classic phenylketonuria (PKU) families.Methods Probands and their family members from three classic PKU families were analyzed by combining linkage analysis through short tandem repeats (STR) polymorphism and PCR-sequencing for the exons within mutation hot spot of phenylalanine hydroxylase gene.Results Linkage analysis found uninformative for Family 1,while 100 % confirmative information was obtained from Family 2 and 3.Sequencing showed compound heterozygous mutations of phenylalanine hydroxylase gene for all of the three probands.Five mutations were detected,namely Y166X,R243Q,R413P,EX6-96A ＞ G and IVS11-1G＞ C,and IVS11-1G ＞ C was a novel identified muntation.Information from linkage analysis and mutation screening showed clearly that the fetus of Family 1 and 2 were affected,while normal for Family 3.Conclusions For those PKU families,reliable service of prenatal genetic diagnosis could be provided by combining linkage analysis with mutation screening of phenylalanine hydroxylase gene.
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The QTc interval is a complex quantitative trait and a strong prognostic indicator of cardiovascular mortality in general, healthy people. The aim of this study was to identify non-genetic factors and quantitative trait loci that govern the QTc interval in an isolated Mongolian population. We used multiple regression analysis to determine the relationship between the QTc interval and non-genetic factors including height, blood pressure, and the plasma lipid level. Whole genome linkage analyses were performed to reveal quantitative trait loci for the QTc interval with 349 microsatellite markers from 1,080 Mongolian subjects. Among many factors previously known for association with the QTc interval, age, sex, heart rate, QRS duration of electrocardiogram and systolic blood pressure were also found to have influence on the QTc interval. A genetic effect for the QTc interval was identified based on familial correlation with a heritability value of 0.31. In a whole genome linkage analysis, we identified the four potential linkage regions 7q31-34, 5q21, 4q28, and 2q36.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Age Factors , Blood Pressure/genetics , Body Height/genetics , Cardiovascular Diseases/genetics , Chromosomes, Human/genetics , Electrocardiography , Genome-Wide Association Study , Heart Rate/genetics , Microsatellite Repeats/genetics , Mongolia/epidemiology , Quantitative Trait Loci/genetics , Sex FactorsABSTRACT
Objective To study the responsible genes of psoriasis vulgaris on chromosome 1q21 in Chinese Han population.Methods Thirty-six families with psoriasis vulgaris,including 92 patients and 98 normal relatives,aged from 12 to 81 years with an average age at 44 years,were enrolled in this study.Blood samples were obtained from all the participants and subjected to DNA extraction.A genome scan was performed with eight microsatellites distributing over chromosome 1q21-1q23.1.Evidence for linkage disequilibrium was assessed with extended transmission disequilibrium test(ETDT)program and Genehunter software.Results Three short tandem repeat markers were found to be associated with psoriasis vulgaris.With Genehunter,evidence for linkage disequilibrium between D1S2345 and psoriasis was found with the NPL value being 1.735(P=0.0329).Moreover,ETDT revealed that the 97-bp allele of D1S2346 and 283-bp allele of D1S484 were preferentially delivered to affected descendants(P＜0.05).Conclusion Chromosome 1q21 contains genes associated with psoriasis vulgaris in Chinese Han population.
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Objective To target the disease gene of disseminated superficial form of porokeratosis (DSP) in a six-generation of a Chinese family including a total of 254 family members in Shandong province. Methods The clinical data and the peripheral blood samples were collected in the pedigree members. The genomic DNA was extracted from the blood samples. A genome-wide scan was performed using 382 pairs of primers labelled with fluorescent stain. The primers were designed for human autosomes. The sequencing results were analyzed by the software of Genescan and Genotype. Linkage analysis was processed by Linkage software package to define the region of disease gene. For fine targeting the disease gene, other 10 micro-satellite markers for the above region were set up for further fine sequencing. Results We obtained the maximum two-point LOD scores of 3.06 at micro-satellite marker D12S78 (recombination fraction ? = 0.00). After fine mapping, the DSP gene is located within a 38.5 cM region between markers D12S326 and D12S79. Conclusion The DSP gene is mapped to chromosome 12q21.2~24.2.
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Objective To identify a locus for hereditary symmetrical dyschromatosis(HSD).Methods A genome-wide scan was performed with402microsatellite markers in two large Chinese HSD families to map the chromosome location of the susceptible gene.The LINKAGE software(Version5.10)and CYRILLIC soft-ware(Version2.01)were used for linkage and haplotype analysis.Results A locus was identified at chro-mosome1q11-1q21with a cumulative maximum two-point LOD score of8.85at microsatellite marker D1S2343(?=0.00).Haplotype analysis indicated that the candidate gene was located within11.6cM region between markers D1S2696and D1S2635.This was the first locus identified for HSD.This study provided a map location for isolation of the candidate genes causing HSD.Conclusion Chromosome1q11-1q21contains the candidate gene susceptible for dyschromatosis symmetrica hereditaria.
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Objective To study the clinical features of hyperkalemic periodic paralysis (hyperKPP) and the relationship with SCN4A gene in a Chinese family Methods The clinical features of 7 patients in a Chinese family with hyperKPP were summarized All 24 exons of SCN4A gene were screened with denaturing high performance liquid chromatography (DHPLC) technology, and then sequence analysis was performed on those with abnormal elution peak Results This family showed typical clinical features of hyperKPP but without myotonia Three mutations were found in exon 13, 23 and 24 respectively Linkage analysis and direct sequencing showed the mutation in exon 24 was a synonymous mutation The mutation in exon 23 was a missense mutation, but proved to be a benign polimophism; the mutation in exon 13 was proved leading to the best known amino acid exchange Thr704Met Conclusion SCN4A gene should be related to hyperKPP, and Thr704Met be responsible for hyperKPP in this Chinese family
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Objective To identify a psoriasis susceptibility locus on chromosome4q in a Chinese Han population.Methods The genome search was performed using12microsatellite spanning chromosome4q in64Chinese Han families(372family members)comprising197affected and175unaffected individuals.GENEHUNTER was used for the parametric and non-parametric linkage analyses.Results(1)Non-paramet-ric linkage analyses:single-point analyses revealed that two adjacent loci on chromosome4q D4S413and D4S1597had evidence of linkage,with NPL-scores of2.04and2.23,and P values of0.021and0.014re-spectively.Multi-point analyses showed a peak NPL-score of3.44and the corresponding P value of0.00056at157.9cM where D4S413located.Moreover,NPL score of more than3was found with a range from155.1cM to172.3cM.(2)Parametric linkage analyses revealed a LOD score of3.70,a heterogeneity LOD score of4.35and a high proportion of linked families(?)of85%under the assumption of a dominant model with dis-ease-allele frequency of0.0062and penetrance of10%at D4S1597.Conclusion Chromosome4q contains genes involved in the susceptibility to psoriasis vulgaris in a Chinese Han population.
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Objective To identify the gene locus and the mutation of DSRAD (double-stranded RNA adenosine deaminase) in a Chinese dyschromatosis symmetrica hereditaria(DSH) family. Methods After confirming the diagnosis of the DSH proband, the genomic DNA was extracted from the whole blood samples of every members of the pedigree. The DSRAD gene intervals were localized by linkage analysis and haplotype reconstruction. The mutation of DSRAD was detected by direct sequencing. Results The candidate gene was localized at the 1q region, consistent with the reported region. The direct sequencing results showed that there was a CAA→TAA transition at exon 2 of DSRAD in all affected family members, which consequently led to a nonsense mutation of Gln517Ter. Conclusion A nonsense mutation is found in the Chinese DSH family.
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Objective To elucidate the genetic base of psoriasis for Chinese patients, the positional candidate loci (D6S273?D6S276?D6S422?D6S299?D6S291?D4S1535?D4S1652?D4S171)previously reported in the regions 6p21.3 and 4q were studied in some carefully examined psoriatic families in order to establish whether the eight reported microsatellites loci(STRs) underlay susceptibility to psoriasis in different populations. Methods Two hundred and five probands with psoriasis vulgaris were identified from outpatients attending the Institute of Dermatology, Chinese Academy of Medical Sciences. Genotypes were generated at 8 polymorphic loci on chromosome 6p21 and 4q in 14 pedigrees. The results were analyzed parametrically by linkage 5.0 software. Results There was evidence for linkage to D6S273 in 6p21.3 (the LOD score was 1.26) . No evidence for linkage was obtained at other loci including three loci on chromosome 4q. Conclusions This study confirms the presence of a psoriasis susceptibility locus on chromosome 6p previously studied. It is shown that there may be psoriasis susceptibility locus D6S273 on chromosome 6p21.3 in the Chinese population.
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Objective:To localize the gene of autosomal dominant retinitis pigmentosa(ADRP) in a family. Methods: A large ADRP family was studied and 3 5 ml of venous blood from some family members was collected, and genomic DNA was extracted from the blood. Then two point linkage analysis between the known markers and the disease locus was performed. Results: Linkage analysis showed the maximum LOD score reached 2.732852 at marker D3S1292 (at recombination fraction ?=0.1). Conclusion: The gene responsible for ADRP is located in 3q21 eara.