Abstract:
:The human gene HIC1 (hypermethylated in cancer) maps to chromosome 17p13.3 and is deleted in the contiguous gene disorder Miller-Dieker syndrome (MDS) [Makos-Wales et al. (1995) Nature Med., 1, 570-577; Chong et al. (1996) Genome Res., 6, 735-741]. We isolated the murine homologue Hic1, encoding a zinc-finger protein with a poxvirus and zinc-finger (POZ) domain and mapped it to mouse chromosome 11 in a region exhibiting conserved synteny to human chromosome 17. Comparison of genomic and cDNA sequences predicts two exons for the murine Hic1. The second exon exhibits 88% identity to the human HIC1 on DNA level. During embryonic development, Hic1 is expressed in mesenchymes of the sclerotomes, lateral body wall, limb and cranio-facial regions embedding the outgrowing peripheral nerves during their differentiation. During fetal development, Hic1 additionally is expressed in mesenchymes apposed to precartilaginous condensations, at many interfaces to budding epithelia of inner organs, and weakly in muscles. We observed activation of Hic1 expression in the embryonic anlagen of many tissues displaying anomalies in MDS patients. Besides lissencephaly, MDS patients exhibit facial dysmorphism and frequently additional birth defects, e.g. anomalies of the heart, kidney, gastrointestinal tract and the limbs (OMIM 247200). Thus, HIC1 activity may correlate with the defective development of the nose, jaws, extremities, gastrointestinal tract and kidney in MDS patients.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Grimm C,Spörle R,Schmid TE,Adler ID,Adamski J,Schughart K,Graw Jdoi
10.1093/hmg/8.4.697subject
Has Abstractpub_date
1999-04-01 00:00:00pages
697-710issue
4eissn
0964-6906issn
1460-2083pii
ddc082journal_volume
8pub_type
杂志文章abstract::Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx279
更新日期:2017-10-15 00:00:00
abstract::The widespread use of persistent organic polybrominated diphenyl ethers (PBDEs) as commercial flame retardants has raised concern about potential long-lived effects on human health. Epigenetic mechanisms, such as DNA methylation, are responsive to environmental influences and have long-lasting consequences. Autism spe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds046
更新日期:2012-06-01 00:00:00
abstract::Missense mutations (K141N and K141E) in the alpha-crystallin domain of the small heat shock protein HSPB8 (HSP22) cause distal hereditary motor neuropathy (distal HMN) or Charcot-Marie-Tooth neuropathy type 2L (CMT2L). The mechanism through which mutant HSPB8 leads to a specific motor neuron disease phenotype is curre...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq234
更新日期:2010-08-15 00:00:00
abstract::The zebrafish has been the model of choice amongst developmental biologists for many years. This small freshwater species offers many advantages to the study of organ and tissue development that are not provided by other model systems. Against this background, modern molecular genetic approaches are being applied to e...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/9.16.2443
更新日期:2000-10-01 00:00:00
abstract::The human genome is often portrayed as consisting of three sequence types, each distinguished by their mode of evolution. Purifying selection is estimated to act on 2.5-5.0% of the genome, whereas virtually all remaining sequence is considered to have evolved neutrally and to be devoid of functionality. The third mode...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddl182
更新日期:2006-10-15 00:00:00
abstract::Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu511
更新日期:2015-02-15 00:00:00
abstract::In vitro fertilization (IVF), blastomere biopsy of the 6-8 cell embryo, and single cell DNA diagnosis allows couples at risk of transmitting an X-linked or autosomal disease to start a pregnancy knowing their child will not be affected. We present a quick and reliable nested PCR strategy for sex determination at the s...
journal_title:Human molecular genetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/hmg/2.8.1187
更新日期:1993-08-01 00:00:00
abstract::Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotid...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt460
更新日期:2014-02-01 00:00:00
abstract::Genetic and environmental influences are thought to interact in their contribution to the etiology of major neuropsychiatric disorders. One of the best replicated findings obtained in genome-wide association studies are genetic variants in the CACNA1C gene. Here, we used our constitutive heterozygous Cacna1c rat model...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz235
更新日期:2019-12-15 00:00:00
abstract::Hay-Wells syndrome, also known as ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (OMIM 106260), is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia, including alopecia, scalp infections, dystrophic nails, hypodontia, ankyloblepharon and cleft lip and/or cleft palate. Th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.3.221
更新日期:2001-02-01 00:00:00
abstract::For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins. Hereditary influences were actually discounted because of a high monozygotic t...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/6.10.1687
更新日期:1997-01-01 00:00:00
abstract::Female aging entails a decline in fertility in mammals, manifested by reduced oocyte reserves and poor oocyte quality accompanied by chromosomal anomalies and reduced litter size. In addition to compromised genetic integrity, recent studies suggest that epigenetic mechanisms may be altered in aging oocytes, with age a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp127
更新日期:2009-06-01 00:00:00
abstract::Pathogenic leucine-rich repeat kinase 2 (LRRK2) mutations are recognized as the most common cause of familial Parkinson's disease in certain populations. Recently, LRRK2 mutations were shown to be associated with a higher risk of hormone-related cancers. However, how LRRK2 itself contributes to cancer risk remains unk...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx337
更新日期:2017-11-15 00:00:00
abstract::Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine (polyQ) tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu522
更新日期:2015-02-15 00:00:00
abstract::The FMR1 gene, associated with fragile X syndrome, has recently been cloned and the sequence of partial cDNA clones is known. We have determined additional cDNA sequences both at the 5' and 3' end. We have characterized the expressed gene by means of RT-PCR in various tissues and have found that alternative splicing t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.4.399
更新日期:1993-04-01 00:00:00
abstract::Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. It remains u...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds038
更新日期:2012-05-15 00:00:00
abstract::Lysosomes, melanosomes and platelet-dense granules are abnormal in the mouse hypopigmentation mutant pearl. The beta3A subunit of the AP-3 adaptor complex, which likely regulates protein trafficking in the trans - Golgi network/endosomal compartments, was identified as a candidate for the pearl gene by a positional/ca...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.2.323
更新日期:1999-02-01 00:00:00
abstract::The X-linked retinitis pigmentosa protein RP2 is a GTPase activating protein (GAP) for the small GTPase Arl3 and both proteins are implicated in the traffic of proteins to the primary cilia. Here, we show that RP2 can facilitate the traffic of the Gβ subunit of transducin (Gβ1). Glutathione S-transferase (GST)-RP2 pul...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr520
更新日期:2012-02-15 00:00:00
abstract::Genomic DNA from 19 Japanese patients with congenital lipoid adrenal hyperplasia (lipoid CAH) representing 16 different families was examined to identify the genetic alterations of steroidogenic acute regulatory protein (StAR). Ten of 19 patients had a 46,XX karyotype and nine had a 46,XY karyotype. Six of the 46,XX p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.4.571
更新日期:1997-04-01 00:00:00
abstract::Mutations in fibroblast growth factor receptors (FGFRs) cause human birth defect syndromes and are associated with a variety of cancers. Although forced expression of mutant activated FGFRs has been shown to oncogenically transform some immortal cell types, their activity in primary cells remains unclear. Here, we sho...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp195
更新日期:2009-07-15 00:00:00
abstract::Alternative splicing emerges as one of the most important mechanisms to generate transcript diversity. It is regulated by the formation of protein complexes on pre-mRNA. We demonstrate that protein phosphatase 1 (PP1) binds to the splicing factor transformer2-beta1 (tra2-beta1) via a phylogenetically conserved RVDF se...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm284
更新日期:2008-01-01 00:00:00
abstract::The 17 genes of the T-box family are transcriptional regulators that are involved in all stages of embryonic development, including craniofacial, brain, heart, skeleton and immune system. Malformation syndromes have been linked to many of the T-box genes. For example, haploinsufficiency of TBX1 is responsible for many...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy146
更新日期:2018-07-15 00:00:00
abstract::Parkinson's disease (PD) is the second most common neurodegenerative disorder in the developed world, and is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Somatic mitochondrial DNA (mtDNA) deletions reach their highest concentration with age in the SN in humans, and may contribut...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds365
更新日期:2012-12-01 00:00:00
abstract::X-linked dilated cardiomyopathy (XLDCM) is a clinical phenotype of dystrophinopathy which is characterized by preferential myocardial involvement without any overt clinical signs of skeletal myopathy. To date, several mutations in the Duchenne muscular dystrophy gene, DMD , have been identified in patients with XLDCM,...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.7.1129
更新日期:1998-07-01 00:00:00
abstract::X-linked dyskeratosis congenita (X-DC) is caused by mutations in the housekeeping nucleolar protein dyskerin. Amino acid changes associated with X-DC are remarkably heterogeneous. Peripheral mononuclear blood cells and fibroblasts isolated from X-DC patients harbor lower steady-state telomerase RNA (TER) levels and sh...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr504
更新日期:2012-02-15 00:00:00
abstract::Recombination, demographic history, drift and selection influence the extent of linkage disequilibrium (LD) in the human genome, but their relative contributions remain unclear. To investigate the effect of meiotic recombination versus population history on LD, three populations with different demographic histories (U...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg008
更新日期:2003-01-01 00:00:00
abstract::Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/dds029
更新日期:2012-05-01 00:00:00
abstract::Forty-nine individuals have been identified with deletions or translocations involving the short arm of chromosome 5. While most display the classical phenotype of the cri-du-chat syndrome, several of the patients do not have the syndrome or have only a subset of the clinical features. Somatic cell hybrids containing ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.2.247
更新日期:1994-02-01 00:00:00
abstract::Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu190
更新日期:2014-09-15 00:00:00
abstract::Muscle-eye-brain disease (MEB), an autosomal recessive disorder prevalent in Finland, is characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. Since the MEB phenotype overlaps substantially with those of Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg syndro...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg043
更新日期:2003-03-01 00:00:00