Abstract:
:Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant syndrome caused by haploinsufficiency of TRPS1 due to point mutations or deletions. Here, we report the first familial TRPS I due to a t(8;13)(q23.3;q21.31) translocation breakpoint <100 kb from the 5' end of TRPS1. Based on the additional abnormalities observed exclusively in the index patient that are mainly compatible with clinical features of TRPS, her phenotype was defined as expanded TRPS I including brain malformations and intellectual disability. Initial analyses did not reveal any genetic defect affecting TRPS1 or any genomic alteration within the breakpoint regions or elsewhere in the genome. The pathogenic chromosome 8q23.3 breakpoint is at position g.116,768,309_116,768,310 within a transposon type I element, 87 kb from the TRPS1 5' end. The 13q21.31 breakpoint is within a tandem repeat region at position g.65,101,509_65,101,510 (genome assembly GRCh37/hg19). This breakpoint is flanked by protocadherin 9 (PCDH9) and protocadherin 20 (PCDH20). As an outcome of the translocation, an evolutionarily conserved non-coding VISTA enhancer element from 13q21.31 is placed within the TRPS1 5' region, 1,294 bp from the breakpoint. The increased expression of TRPS1 found by three independent methods is most probably translocation allele derived and driven by the translocated enhancer element. The index patient's expanded phenotype presumably involves the epithelial-to-mesenchymal transition pathway that may be due to TRPS1 overexpression. Together, these findings support that the reported translocation-associated phenotypes are "cis-ruption" and TRPS1 overexpression related, the latter most probably caused by the novel enhancer element in the TRPS1 5' region.
journal_name
Hum Genetjournal_title
Human geneticsauthors
David D,Marques B,Ferreira C,Araújo C,Vieira L,Soares G,Dias C,Pinto Mdoi
10.1007/s00439-013-1333-0subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1287-99issue
11eissn
0340-6717issn
1432-1203journal_volume
132pub_type
杂志文章相关文献
HUMAN GENETICS文献大全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::Eukaryotic genomes contain 5-methylcytosine (5mC) as a rare base.5mC arises by postsynthetic modification of cytosine and occurs, at least in animals, predominantly in the dinucleotide CpG. The base is not distributed randomly in these genomes but conforms to a pattern. This pattern varies between taxa but appears to ...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/BF00292363
更新日期:1983-01-01 00:00:00
abstract::One of the central goals of human genetics is the identification of loci with alleles or genotypes that confer increased susceptibility. The availability of dense maps of single-nucleotide polymorphisms (SNPs) along with high-throughput genotyping technologies has set the stage for routine genome-wide association stud...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-008-0522-8
更新日期:2008-08-01 00:00:00
abstract::An increased incidence of cystic fibrosis (CF) has been reported in some populations of Native Americans of the Southwest such as the Pueblo, which is a genetic isolate. As the most common mutation found in Caucasians (delta F508) was absent and only one chromosome carried the G542X mutation, we decided to analyze the...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00206956
更新日期:1994-12-01 00:00:00
abstract::A series of 195 random chromosome 22-specific probes, equivalent to approximately 1% of the size of this chromosome, have been isolated from a chromosome 22-specific bacteriophage lambda genomic library. These probes were mapped to four different regions of chromosome 22 on a panel of five somatic cell hybrids. Restri...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00200562
更新日期:1990-02-01 00:00:00
abstract::Salla disease is an inherited lysosomal storage disorder caused by accumulation of free sialic acid in the lysosomes. Lamp genes, lamp A and lamp B (lysosome associated membrane proteins), are the first known genes encoding for human lysosomal membrane proteins. Absence of linkage in a large group of families shows th...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00204936
更新日期:1991-11-01 00:00:00
abstract::Experiments have been performed to determine whether human lymphocytes in primary cultures can show an "adaptive" response to the induction of cellular lesions (manifested as a production of sister chromatid exchanges, SCEs) as previously found in bacteria and established human and mammalian cell lines. Human lymphocy...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00292670
更新日期:1986-05-01 00:00:00
abstract::Postprandial triglyceridemia is an emerging risk factor for cardiovascular disease. However, most of the genes that influence postprandial triglyceridemia are not known. We evaluated whether a common nonsynonymous SNP rs1260326/P446L in the glucokinase regulatory protein (GCKR) gene influenced variation in the postpra...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-009-0700-3
更新日期:2009-10-01 00:00:00
abstract::To improve the analysis of parentage testing with the additional technique of DNA polymorphisms, the usefulness of probe YNH24 was studied. The allele frequency distribution of restriction fragments detected by probe YNH24 on TaqI-digested genomic DNA from 100 unrelated individuals was determined. For this purpose, th...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00196240
更新日期:1990-03-01 00:00:00
abstract::Various genetic loci harboring oncogenes, tumor suppressor genes, and genes for calcium receptors have been implicated in the development of parathyroid tumors. We have carried out loss of heterozygosity (LOH) studies in chromosomes 1p, 1q, 3q, 6q, 11q, 13q, 15q, and X in a total of 89 benign parathyroid tumors. Of th...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050369
更新日期:1997-03-01 00:00:00
abstract::The Great Lakes lie within a region of East Africa with very high human genetic diversity, home of many ethno-linguistic groups usually assumed to be the product of a small number of major dispersals. However, our knowledge of these dispersals relies primarily on the inferences of historical, linguistics and oral trad...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-015-1583-0
更新日期:2015-09-01 00:00:00
abstract::Extensive studies that have sought causative mutation(s) for neural tube defects (NTDs) have yielded limited positive findings to date. One possible reason for this is that many studies have been confined to analyses of germline mutations and so may have missed other, non-germline mutations in NTD cases. We hypothesiz...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-020-02172-0
更新日期:2020-10-01 00:00:00
abstract::Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of D4Z4 repeat on 4q35. It displays a remarkable inter- and intra-familial clinical variability ranging from severe phenotype to asymptomatic carriers. Mosaicism for the contracted FSHD-sized allele is a recurrent finding,...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-0100-2
更新日期:2006-03-01 00:00:00
abstract::Two cases of primary ring chromosome 2 and one case of a ring secondary to a paternal 2/6 translocation are described and compared with a fourth case of ring 2 from the literature. The breakpoints in two cases are identical and the same as the breakpoint on chromosome 2 in the composite 2/6 ring. The three primary rin...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00286899
更新日期:1979-04-27 00:00:00
abstract::Three children with hyperphenylalaninaemia and hyperphenylalaninaemic mothers are presented. At least one of the affected children was a compound heterozygote for hyperphenylalaninaemia and phenylketonuria. The families were examined by an L-phenylalanine loading test, by direct determination of phenylalanine hydroxyl...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291569
更新日期:1984-01-01 00:00:00
abstract::The CDY family of genes is of special interest because some of them are included in chromosome-Y microdeletions detected among infertile men and are apparently involved in the spermiogenetic process. In this study, we employed the reverse transcriptase/polymerase chain reaction technique to test the RNA expression of ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-003-0990-9
更新日期:2003-11-01 00:00:00
abstract::In certain segments of human DNA, the methylation of deoxycytidine residues has been found to be highly specific and interindividually conserved. Imprinted DNA sequences in diploid primary cells show allele-specific differences in DNA methylation, usually with the active chromosomal regions being unmethylated and the ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00202872
更新日期:1994-08-01 00:00:00
abstract::Despite the identification of an increasing number of genes involved in sex determination and differentiation, no cause can be attributed to most cases of 46, XY gonadal dysgenesis, approximately 20% of 46, XX males and the majority of subjects with 46, XX true hermaphroditism. Perhaps the most interesting candidate f...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000428
更新日期:2000-12-01 00:00:00
abstract::The recent discovery that the extra chromosome in about 30% of cases of 47, trisomy 21 is of paternal origin has revived interest in the possibility of paternal age as a risk factor for a Down syndrome birth, independent of maternal age. Parental age distribution for 611 Down's syndrome 47, +21 cases was studied. The ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291534
更新日期:1983-01-01 00:00:00
abstract::We have investigated the origin of rapidly adhering (RA) cells in three cases of neural tube defects (two anencephali, one encephalocele). We were able to demonstrate the presence of glial fibrillary acidic (GFA) protein in variable percentages (4--80%) of RA cells cultured for 4--6 days by use of indirect immunofluor...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00274694
更新日期:1981-01-01 00:00:00
abstract::We have studied the incidence of alpha-thalassemia in normal and SS individuals from Senegal, Benin, Upper Volta, and Central Republican Africa. The alpha thal gene frequency is not significantly different in the controls from the various populations and in the SS patients from Senegal. In contrast it is compatible wi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00292592
更新日期:1984-01-01 00:00:00
abstract::Restriction endonucleases have been recently proved to be active on fixed chromosomes, thus they are useful in chromatin structure studies. Within this class of enzymes, Alu I is able to detect the presence and localization of highly repetitive DNA sequences in human and in other mammalian and dipteran species. In thi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291894
更新日期:1986-03-01 00:00:00
abstract::Accessory auricular anomaly is a small excrescence of skin that contains elastic cartilage on different regions of the helix and the face. Previous work has shown that the genetic trait of some patients with the isolated symptom of accessory auricular anomaly is autosomal dominant. To map the gene for autosomal domina...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0206-1
更新日期:2006-08-01 00:00:00
abstract::Cytogenetic studies were carried out on 150 oocytes obtained in a human in vitro fertilization (IVF) program. Although all cells lacked signs of fertilization at light microscopy, 46 (30.7%) appeared to show cytological evidence of fertilization. At least one-third of these cells (with development arrested before firs...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00283693
更新日期:1989-03-01 00:00:00
abstract::A 45,X male individual was shown to have a translocation of Y-chromosome material to the short arm or proximal long arm of chromosome 15. This translocation was detected by genomic DNA blotting and in situ hybridization with Y-chromosome-specific DNA probes. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00280488
更新日期:1986-12-01 00:00:00
abstract::To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 8...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390100525
更新日期:2001-06-01 00:00:00
abstract::Experiments were performed in order to gain information about the primary process leading to the production of sister chromatid exchanges (SCEs). Radical-forming substances (hydroxylamine, hydrazine and the antituberculous drug isoniazid) were examined for their effectiveness in inducing SCEs. All three substances pro...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278964
更新日期:1980-01-01 00:00:00
abstract::Most genetic studies recruit high risk families and the discoveries are based on non-random selected groups. We must consider the consequences of this ascertainment process in order to apply the results of genetic research to the general population. In previous reports, we developed a latent variable model to assess t...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0147-8
更新日期:2006-05-01 00:00:00
abstract::Using dual-laser sorted chromosomes and spot-blot analysis, we have previously assigned genomic DNA sequences coding for human alpha 1 (IV) procollagen to chromosome 13 (Pihlajaniemi et al. 1985). By in situ hybridization to normal chromosomes and chromosomes with 13q deletions, we now report the localization of this ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00282074
更新日期:1986-10-01 00:00:00
abstract::ATP-sensitive K+ (K(ATP)) channels maintain cardiac homeostasis under stress, as revealed by murine gene knockout models of the KCNJ11-encoded Kir6.2 pore. However, the translational significance of K(ATP) channels in human cardiac physiology remains largely unknown. Here, the frequency of the minor K23 allele of the ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-009-0731-9
更新日期:2009-12-01 00:00:00