Abstract:
:Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). We performed mutation screening in a group of 20 patients, identyifing 28 mutations, 14 of which were novel (L35F, 204delC, 221insGCGCG, G82D, W156C, 507delC, IVS3+1G-->A, E336X, V501G, R520W, S534Y, W649C, 1953insGCCA, 2185delAGA). Four of these mutations were found in homozygosity and only one was seen in two different patients, showing the remarkable molecular heterogeneity of the disease. Mutation IVS3+1G-->A produces aberrant RNA splicing: it represents a base substitution from G to A of the invariant GT dinucleotides at the splicing donor site of intron 3 resulting in the skipping of exon 3 and both exons 2 and 3. Transient transfection of COS cells, by DNA mutagenized with NAGLU mutations, produced enzymatic molecules without activity, demonstrating the deleterious nature of the defects. Metabolic labeling of transfected mutants suggested a normal synthesis of the involved polypeptide for missense alterations, whereas increased protein or mRNA instability was shown for nonsense and most of the frameshift mutations.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Tessitore A,Villani GR,Di Domenico C,Filocamo M,Gatti R,Di Natale Pdoi
10.1007/s004390000429keywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
568-76issue
6eissn
0340-6717issn
1432-1203journal_volume
107pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::In this study, we performed an in-depth analysis of the neurologic and ophthalmologic phenotype in a patient with Pitt-Hopkins syndrome (PTHS), a disorder characterized by severe mental and motor retardation, carrying a uniallelic TCF4 deletion, and studied a zebrafish model. The PTHS-patient was characterized by high...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-0999-4
更新日期:2011-11-01 00:00:00
abstract::The von Willebrand factor pseudogene, previously mapped to chromosome 22, was sublocalized by in situ hybridization using as probe a von Willebrand factor cDNA fragment completely contained in the pseudogenic region. Chromosome spreads were from a patient carrying a unique balanced de novo translocation 46,X,t(X;22)(p...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00285168
更新日期:1989-10-01 00:00:00
abstract::Chromosome analysis of G-banded cells from nine individuals showed that 9qh+ chromosomes have an extra band in the h region in approx. 3 to 50% of the cells. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278832
更新日期:1978-09-19 00:00:00
abstract::A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3' end of exon 11. The wild-type sequence, CTCAG, was deleted ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050826
更新日期:1998-09-01 00:00:00
abstract::Two antitubercular drugs, viz., isoniazid (INH) and para-aminosalicylic acid (PAS), in combination, were evaluated for their in vivo clastogenic effects of human lymphocyte chromosomes. Lymphocyte cultures from tuberculosis patients taking a therapeutic dose of INH and PAS for a period of not less than 3 months and fr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00274696
更新日期:1981-01-01 00:00:00
abstract::Starting from a group of 265 Italian patients affected with Duchenne or Becker muscular dystrophy a screening for duplications in the dystrophin gene was performed on 112 cases in which no deletions had previously been detected. The 21 intragenic duplications detected account for 7.9% of the total. Among these, one du...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02272848
更新日期:1994-07-01 00:00:00
abstract::Despite the recent discover of genome-editing methods, today we can say these approaches have firmly entered our life. Two approaches-knocking out malfunctioning gene allele or correcting the mutation with precise knock-in-can be used in hereditary monogenic diseases treatment. The latter approach is relatively ineffe...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-018-1953-5
更新日期:2019-01-01 00:00:00
abstract::Three fragile sites 2q13, 12q13, and 17p12 were found in one family. In the index case, who was first investigated in 1969 for low birth weight and bilateral inguinal hernia, three tissues were examined, blood, marrow, and skin. Three of the family have been reinvestigated after 17 years. Cultures for sister chromatid...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291608
更新日期:1986-06-01 00:00:00
abstract::An easy-to-use, simulation-based power calculator (ASP) for linkage analysis using sib-pair designs (concordant or discordant) has been developed and made publicly available via the Internet. The program employs a diallelic model for the trait locus, at which parental/offspring genotypes are simulated, assuming Hardy-...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-001-0634-x
更新日期:2001-12-01 00:00:00
abstract::Severe combined immunodeficiency (SCID) is caused by a variety of underlying defects. Approximately 40% of cases are thought to be of the X-linked type (SCIDX1), which is phenotypically characterised by the absence, or very low numbers, of T cells, but normal or even high B cell numbers. The gene responsible for SCIDX...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050428
更新日期:1997-05-01 00:00:00
abstract::Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-020-02248-x
更新日期:2021-01-12 00:00:00
abstract::It has been reported that studies of the genetic consequences of inbreeding should adopt a different strategy in populations having a relatively old inbreeding history and where inbreeding levels have varied over time. This contention is tested with a series of 39,495 single-birth records from Bombay, India, collected...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00390435
更新日期:1977-04-07 00:00:00
abstract::It is shown by discontinuous sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis of human red cell membranes, followed by periodic acid Schiff (PAS) staining and densitometry, that the band PAS-3 (monomeric Ss glycoprotein) exhibits a polymorphism with respect to its staining intensity. In membranes of the ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291494
更新日期:1976-05-19 00:00:00
abstract::The marriage rate of epileptic patients was 62% in males and 78% in females. Compared with the rates in the general population, the male patients had a 15% lower rate, but there was no difference in females. There were 263 patients with at least one offspring selected for the study. There were 234 sons and 272 daughte...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00273256
更新日期:1977-04-15 00:00:00
abstract::The pattern of X-chromosome inactivation was analyzed, by means of two different DNA probes (pSPT-PGK and M27 beta), in several cell lineages derived from females belonging to a pedigree with X-linked immunodeficiency with hyper-IgM (HIGM1). Non-random X-chromosome inactivation was demonstrated in T cells, B cells, an...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00206059
更新日期:1991-12-01 00:00:00
abstract::We identified two additional mutations in the ferrochelatase gene in two Swiss patients with erythropoietic protoporphyria (EPP). Ferrochelatase cDNA from patients was amplified by the polymerase chain reaction (PCR) and subjected to mutation analysis by sequencing PCR products either directly or after subcloning. The...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201578
更新日期:1994-06-01 00:00:00
abstract::In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00286513
更新日期:1984-01-01 00:00:00
abstract::Dermatoglyphics of 11 patients with Wilson's disease and 16 of their clinically asymptomatic relatives of first degree were investigated; 11 of the latter ones were heterozygous in agreement with the turn over rates of Cu-67, 12 under the assumption of autosomal recessive inheritance. On the finger tips the Mb. Wilson...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00296148
更新日期:1976-02-29 00:00:00
abstract::A total of 15,387 individuals living in Hiroshima and Nagasaki, of whom 10,864 are unrelated, were examined for erythrocyte triosephosphate isomerase (TPI) by starch gel electrophoresis using TEMM buffer, pH 7.4. Four kinds of new variants, one having a cathodal migration and three having anodal migrations, were encou...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00279312
更新日期:1984-01-01 00:00:00
abstract::Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by mutations in the ATM gene. The ATM gene spans more than 150 kb at chromosomal region 11q23.1 and encodes a product of 3,056 amino acids. The ATM protein is a serine/threonine protein kinase and is involved in oxidative stress, cell cycle control,...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-1254-7
更新日期:2005-07-01 00:00:00
abstract::A fragile site on chromosome 12, at 12q24.13, was found in the lymphocytes of two members of a family during the study for detection of a fragile X chromosome. The site was found to be heritable and folate-sensitive, and it fulfills all four criteria for a fragile site. It thus can now be confirmed as the heritable fr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00273829
更新日期:1987-01-01 00:00:00
abstract::A simple and rapid technique is described whereby the nucleolus organizer regions (NORs) of human chromosomes can be differentially stained with silver. This staining is followed by trypsin-Giemsa banding on the same metaphase chromosomes. The metaphases simultaneously exhibit silver-stained NORs and G bands, allowing...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00396478
更新日期:1978-07-12 00:00:00
abstract::We have analyzed the allele frequency distribution at the highly polymorphic variable number of tandem repeat (VNTR) locus D1S80 (pMCT118) in seven ethnic populations (namely, New Guinea Highlanders of Papua New Guinea, Dogrib Indians of Canada, Pehuenche Indians of Chile, American and Western Samoans, Kacharis of Nor...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00208279
更新日期:1994-09-01 00:00:00
abstract::Rapid progress in the sequencing of the genome of man and other species allows for the comparative analysis of their genetic structure and content. We have used a combined biochemical and computer-based approach to characterize a 146 kb human genomic bacterial artificial chromosome clone from chromosome 5q13 and disco...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-001-0610-5
更新日期:2001-11-01 00:00:00
abstract::A ring chromosome No. 13 was found in a 21-year-old female with multiple anomalies suggestive of 13q--syndrome. Chromosomes of the girl and her parents, studied by quinacrine staining, revealed the ring to be of paternal origin. Detailed study of the quinacrine banding pattern of the ring indicated loss of the most di...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00281894
更新日期:1976-07-27 00:00:00
abstract::A severely growth-retarded female newborn is described, who dies a few hours after birth. About half of the clones and metaphases from an amniotic fluid cell culture (set up at 35th week of gestation) and only 1/27 of the metaphases from a blood lymphocyte culture contained an additional No. 22 chromosome. Abnormal fi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00274677
更新日期:1981-01-01 00:00:00
abstract::By analyzing c-myc specific fragments from white blood cell DNAs of 98 gastric cancer patients and 46 control subjects, we observed 6 unexpected patterns due to presence of a variant c-myc gene in addition to the normal gene. Restriction enzyme mapping indicated that the variant c-myc gene was the result of a 5' delet...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00209016
更新日期:1991-09-01 00:00:00
abstract::Heritability, the fraction of phenotypic variation explained by genetic variation, has been estimated for many phenotypes in a range of populations, organisms, and time points. The recent development of efficient genotyping and sequencing technology has led researchers to attempt to identify the genetic variants respo...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-012-1199-6
更新日期:2012-10-01 00:00:00
abstract::Mitochondrial DNA (mtDNA) haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian mitochondrial haplogroup lineages. Usi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-014-1421-9
更新日期:2014-07-01 00:00:00
abstract::Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases ...
journal_title:Human genetics
pub_type: 杂志文章,meta分析
doi:10.1007/s00439-007-0431-2
更新日期:2007-12-01 00:00:00