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 missense mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation. Furthermore, an individual with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three individuals with point mutations revealed deregulation of genes involved in signal transduction and emphasized the role of CTCF in enhancer-driven expression of genes. Our findings indicate that haploinsufficiency of CTCF affects genomic interaction of enhancers and their regulated gene promoters that drive developmental processes and cognition.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Gregor A,Oti M,Kouwenhoven EN,Hoyer J,Sticht H,Ekici AB,Kjaergaard S,Rauch A,Stunnenberg HG,Uebe S,Vasileiou G,Reis A,Zhou H,Zweier Cdoi
10.1016/j.ajhg.2013.05.007subject
Has Abstractpub_date
2013-07-11 00:00:00pages
124-31issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(13)00220-6journal_volume
93pub_type
杂志文章abstract：:To resolve uncertainty concerning the inheritance of the perinatal lethal form of osteogenesis imperfecta (OI type II), we collected family data and radiographs for 71 probands and analyzed the collagens synthesized by dermal fibroblastic cells cultured from 43 of the probands, 19 parental pairs, and single parents of...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:In this paper we present linkage results from the analysis of 18 Utah breast cancer kindreds, for three 17q markers. Four kindreds had LOD scores greater than 1.0 for at least one of the marker loci. One of these kindreds has a LOD score of 6.07 with D17S579, and we believe it to be the most informative 17q family rep...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:New human mutations are thought to originate in germ cells, thus making a recurrence of the same mutation in a sibling exceedingly rare. However, increasing sensitivity of genomic technologies has anecdotally revealed mosaicism for mutations in somatic tissues of apparently healthy parents. Such somatically mosaic par...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.07.003
更新日期：2014-08-07 00:00:00
abstract：:Genome regions containing multiple copies of homologous genes, such as the immunoglobulin (Ig) heavy-chain constant-region (IGHC) locus, are often unstable and give rise to duplicated and deleted haplotypes. Analysis of such processes is fundamental to understanding the mechanisms of evolution of multigene families. I...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnorm...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：
更新日期：1989-08-01 00:00:00
abstract：:X chromosome- and Y chromosome-specific DNA probes were used to study different aspects of the genesis of sex-chromosome monosomy. Using X-linked RFLPs, we studied the parental origin of the single X chromosome in 35 spontaneously aborted and five live-born 45,X conceptions. We determined the origin in 35 cases; 28 ha...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
abstract：:Most sporadic cases of retinoblastoma, malignant eye tumor of children, may require the identification of a mutation of the retinoblastoma gene (RB1 gene) for precise genetic counseling. We established a mutation detection system of and screened for the RB1 gene mutation in 24 patients with retinoblastoma--12 bilatera...
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：: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：:The gene for human apolipoprotein C2 (APOC2), situated on the proximal long arm of chromosome 19, is closely linked to the gene for the most common form of adult muscular dystrophy, myotonic dystrophy (DM). Six APOC2 RFLPs (TaqI, BglI, BanI, BamHI, NcoI, and AvaII) have been identified to date. We have conducted a com...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301872
更新日期：1998-06-01 00:00:00
abstract：:Allele-specific replication differences have been observed in imprinted chromosomal regions. We have exploited this characteristic of an imprinted region by using FISH at D15S9 and SNRPN (small nuclear ribonucleo protein N) on interphase nuclei to distinguish between Angelman and Prader-Willi syndrome patient samples ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Culture of human amniotic-fluid cells from cases of fetal neural tube defects produces a population of rapidly adhering cells that were initially thought to be macrophages and later interpreted to be of neural origin. In this study double and triple labeling systems for the simultaneous detection of glial and macropha...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.06.006
更新日期：2014-07-03 00:00:00
abstract：:Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subs...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.06.006
更新日期：2008-07-01 00:00:00
abstract：:Six closely linked PRP (proline-rich protein) genes code for many salivary PRPs that show frequent length and null variants. From determined protein sequences and DNA sequence analysis of variant alleles, we here report the coding and molecular basis for Con (concanavalin A-binding) and Po (parotid "o") protein polymo...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.12.001
更新日期：2017-02-02 00:00:00
abstract：:Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1086/425285
更新日期：2004-11-01 00:00:00
abstract：:We recently reported a two-stage genomewide screen of 48 sib pairs affected with intracranial aneurysms (IAs) that revealed suggestive linkage to chromosome 19q13, with a LOD score of 2.58. The region supporting linkage spanned approximately 22 cM. Here, we report a follow-up study of the locus at 19q13, with a sample...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/382285
更新日期：2004-03-01 00:00:00
abstract：:Nine markers from the pericentromeric region of chromosome 17 were typed in 16 British and five South African families with neurofibromatosis type 1 (NF1). The markers--p17H8, pHHH202, and EW204--were linked to NF1 at recombination fractions less than 1%. No evidence of locus heterogeneity was detected. Inspection of ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Aberrant gene expression underlies many human diseases. RNA polymerase II (Pol II) pausing is a key regulatory step in transcription. Here, we mapped the locations of RNA Pol II in normal human cells and found that RNA Pol II pauses in a consistent manner across individuals and cell types. At more than 1,000 genes inc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.08.003
更新日期：2019-10-03 00:00:00
abstract：:Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.02.001
更新日期：2011-03-11 00:00:00
abstract：:We have previously described a syndrome characterized by facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs (FDLAB, or Traboulsi syndrome). In view of the consanguineous nature of the affected families and the likely autosomal-recessive inheritance pattern of this syn...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.04.002
更新日期：2014-05-01 00:00:00
abstract：:Huntington disease (HD) is a dominantly inherited neurodegenerative disorder characterized by dysregulation of various genes. Recently, microRNAs (miRNAs) have been reported to be involved in this dysregulation, suggesting that manipulation of appropriate miRNA regulation may have a therapeutic benefit. Here, we repor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.05.025
更新日期：2013-08-08 00:00:00
abstract：:To detect heterozygotes for maple-syrup-urine disease (MSUD), activities of branched-chain-alpha-ketoacid (BCKA) dehydrogenase and its components in skin fibroblasts of two obligatory heterozygotes and amnion cells of a fetus at risk were measured. Intact heterozygous cells were found to decarboxylate [1-14C] alpha-ke...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:The term "duty to recontact" refers to the possible ethical and/or legal obligation of genetics service providers (GSPs) to recontact former patients about advances in research that might be relevant to them. Although currently this practice is not part of standard care, some argue that such an obligation may be estab...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302293
更新日期：1999-03-01 00:00:00
abstract：:We have developed a technique called "LSSP-PCR" (low-stringency single specific primer PCR) that detects single or multiple mutations in DNA. A purified DNA fragment is submitted to PCR by using a single primer specific for one of the extremities of the fragment, under conditions of very low stringency. The primer hyb...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at position 12320 affects the T psi C loop at a conserved site and was not found in 120 controls. Analysis of cultured fibroblasts, white blood cells/platelets,...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving approximately 30% of alleles undetected. Nevertheless, very few exhaustive methods have b...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301969
更新日期：1998-08-01 00:00:00
abstract：:Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-08-01 00:00:00
