Abstract:
:Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a serious and potentially fatal inherited defect in the beta-oxidation of fatty acids. Approximately 80% of patients with MCAD deficiency are homozygous for a single disease-causing mutation (G985). The remaining patients (except for a few cases worldwide) are compound heterozygous with G985 in one allele. By sequencing of cloned PCR-amplified MCAD cDNA from a G985 compound heterozygous patient, we identified a C-to-T transition at position 157 as the only change in the entire coding sequence of the non-G985 allele. The presence of the T157 mutation was verified in genomic DNA from the patient and her mother by a PCR-based assay. The mutation changes conserved arginine at position 28 (R28C) of the mature MCAD protein. The effect of the T157 mutation on MCAD protein was investigated by expression of mutant MCAD cDNA in COS-7 cells. On the basis of knowledge about the three-dimensional structure of the MCAD protein, we suggest that the mutation destroys a salt bridge between arginine28 and glutamate86, thereby affecting the formation of enzymatically active protein. Twenty-two additional families with compound heterozygous patients were tested in the PCR-based assay. The T157 mutation was identified in one of these families, which had an MCAD-deficient child who died unexpectedly in infancy. Our results indicate that the mutation is rare. It is, however, noteworthy that a homologous mutation has previously been identified in the short-chain acyl-CoA dehydrogenase (SCAD) gene of a patient with SCAD deficiency, suggesting that the conserved arginine is crucial for formation of active enzyme in the straight-chain acyl-CoA dehydrogenases.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Andresen BS,Bross P,Jensen TG,Winter V,Knudsen I,Kølvraa S,Jensen UB,Bolund L,Duran M,Kim JJsubject
Has Abstract,Author List Incompletepub_date
1993-09-01 00:00:00pages
730-9issue
3eissn
0002-9297issn
1537-6605journal_volume
53pub_type
杂志文章abstract::A novel technique for detecting electrophoretic and quantitative variants of group-specific component (Gc) proteins is described. The technique, in vitro labeling with radioactive vitamin D followed by polyacrylamide gel electrophoresis and autoradiography (PAGE autoradiography), permits sensitive, high resolution det...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract::Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::Genetic risks are usually computed under the assumption that genetic parameters, such as the recombination fraction, are known without error. Uncertainty in the estimates of these parameters must translate into uncertainty regarding the risk. To allow for uncertainties in parameter values, one may employ Bayesian tech...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::The transmission/disequilibrium test (TDT) originally was introduced to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Recently, the TDT has been used to test for association in the presence of linkage. The motivation for this is that linkage analysis typi...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/514860
更新日期:1997-08-01 00:00:00
abstract::Fibroblast growth factor homologous factors (FHFs) are intracellular proteins which regulate voltage-gated sodium (Nav) channels in the brain and other tissues. FHF dysfunction has been linked to neurological disorders including epilepsy. Here, we describe two sibling pairs and three unrelated males who presented in i...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.10.017
更新日期:2021-01-07 00:00:00
abstract::Functional characterization of a gene often requires the discovery of the full spectrum of its associated phenotypes. Mutations in the human GLI3 gene have been identified in Greig cepalopolysyndactyly, Pallister-Hall syndrome (PHS), and postaxial polydactyly type-A (PAP-A). We studied the involvement of GLI3 in addit...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302557
更新日期:1999-09-01 00:00:00
abstract::To identify Chinese geneticists' views of ethical issues in genetic testing and screening, a national survey was conducted. Of 402 Chinese geneticists asked to participate, 255 (63%) returned by mail anonymous questionnaires. The majority of respondents thought that genetic testing should be offered in the workplace f...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302020
更新日期:1998-09-01 00:00:00
abstract::About 70 individuals from Punjab were examined for some mtDNA polymorphisms, namely, the RFLPs of the six classical enzymes (HpaI, BamHI, HaeII, MspI, AvaII, and Hin-cII) and for the sites AluI(7,025), DdeI(10,394), and AluI(10,397). The AluI(7,025) polymorphic site was also investigated in 96 Indians from Uttar Prade...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Regional chromosomal mosaicism has been found in tissue from the clitoral mass of an infant presenting with ambiguous genitalia. Chromosome analysis of skin from the clitoral mass was interpreted as 46,XX/52,XX, +2, +7, +8, +12, +13, +20, whereas study of ovarian tissue and peripheral lymphocytes found each to have no...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset < 60 years), and late-onset families. A genetic association was observed between apolipo...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic va...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/498175
更新日期:2005-12-01 00:00:00
abstract::Mitochondrial genetics is complicated by heteroplasmy, or mutant load, which may be from 1%-99%, and thus may produce a gene dosage-type effect. Limited data are available for genotype/phenotype correlations in disorders caused by mtDNA mutations; therefore, prenatal diagnosis for mtDNA mutations has been hindered by ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302488
更新日期:1999-08-01 00:00:00
abstract::Although intensive efforts have been undertaken to elucidate the genetic background of immunoglobulin A nephropathy (IgAN), genetic factors associated with the pathogenesis of this disease are still not well understood. We designed a case-control association study that was based on linkage disequilibrium among single-...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339077
更新日期:2002-03-01 00:00:00
abstract::In the present study, we report a kindred with hearing loss, congenital heart defects, and posterior embryotoxon, segregating as autosomal dominant traits. Six of seven available affected patients manifested mild-to-severe combined hearing loss, predominantly affecting middle frequencies. Two patients were diagnosed w...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/341327
更新日期:2002-07-01 00:00:00
abstract::The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2007.12.011
更新日期:2008-03-01 00:00:00
abstract::The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the und...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.06.029
更新日期:2016-09-01 00:00:00
abstract::The phosphatase activity of bisphosphoglyceromutase (DPGM) was used to determine the phenotypes of the enzyme. DPGM was polymorphic in four Alaskan ethnic groups. ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::HLA class II loci are useful markers in human population genetics, because they are extremely variable and because new molecular techniques allow large-scale analysis of DNA allele frequencies. Direct DNA typing by hybridization with sequence-specific oligonucleotide probes (HLA oligotyping) after enzymatic in vitro P...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::Utilizing a fluorescent technique for the localization of transglutaminase activity after electrophoresis on thin layer agarose gels, we observed a new polymorphism of coagulation factor XIII in both platelets and plasma. The electrophoretic pattern was that of a dimeric protein. Homozygotes gave a single band, while ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo m...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.05.007
更新日期:2013-07-11 00:00:00
abstract::Analysis of human-Chinese hamster somatic cell hybrids with spontaneously derived chromosome structural changes has provided data for the regional and subregional localization of gene loci which have previously been assigned to human chromosomes 2, 12, and X. Correlation of the expression of human gene loci with the h...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1975-09-01 00:00:00
abstract::We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 × 10(-8)) in our ...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2012.01.010
更新日期:2012-03-09 00:00:00
abstract::Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation that is characterized, in male patients, by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological hand aspects exhibited by patients are essential clues for the diag...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/340607
更新日期:2002-06-01 00:00:00
abstract::Deletions of the distal short arm of chromosome 1 (1p36) represent a common, newly delineated deletion syndrome, characterized by moderate to severe psychomotor retardation, seizures, growth delay, and dysmorphic features. Previous cytogenetic underascertainment of this chromosomal deletion has made it difficult to ch...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/515520
更新日期:1997-09-01 00:00:00
abstract::Animal microRNAs (miRNAs) regulate gene expression through base pairing to their targets within the 3' untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. We mapped annotated SNPs onto a collection of experimentally sup...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/519979
更新日期:2007-08-01 00:00:00
abstract::Duplications of proximal 15q have been found in individuals with autistic disorder (AD) and varying degrees of mental retardation. Often these abnormalities take the form of a supernumerary inverted duplicated chromosome 15, more properly described as an isodicentric chromosome 15, or idic(15). However, intrachromosom...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302999
更新日期:2000-08-01 00:00:00
abstract::Studies in mouse and chick have shown that the 5' HoxD genes play major roles in the development of the limbs and genitalia. In humans, mutations in HOXD13 cause the dominantly inherited limb malformation synpolydactyly (SPD). Haploinsufficiency for the 5' HOXD genes has recently been proposed to underlie the monodact...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338921
更新日期:2002-02-01 00:00:00
abstract::About 20%-25% of Caucasian individuals are nonsecretors who fail to express soluble A, B, H, and Lewis b histo-blood group antigens in secretory organs and secretory fluids because of the absence of the Secretor gene (FUT2)-encoded alpha(1,2)-fucosyltransferase (Se enzyme) activity. Recently, the FUT2 and a pseudogene...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00