Abstract:
:Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Coppinger J,McDonald-McGinn D,Zackai E,Shane K,Atkin JF,Asamoah A,Leland R,Weaver DD,Lansky-Shafer S,Schmidt K,Feldman H,Cohen W,Phalin J,Powell B,Ballif BC,Theisen A,Geiger E,Haldeman-Englert C,Shaikh TH,Saitta S,doi
10.1093/hmg/ddp042subject
Has Abstractpub_date
2009-04-15 00:00:00pages
1377-83issue
8eissn
0964-6906issn
1460-2083pii
ddp042journal_volume
18pub_type
杂志文章abstract::Lafora progressive myoclonus epilepsy, caused by defective laforin or malin, insidiously present in normal teenagers with cognitive decline, followed by rapidly intractable epilepsy, dementia and death. Pathology reveals neurodegeneration with neurofibrillary tangle formation and Lafora bodies (LBs). LBs are deposits ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi306
更新日期:2005-09-15 00:00:00
abstract::We studied a consanguineous Palestinian Arab family segregating an autosomal recessive progressive myoclonus epilepsy (PME) with early ataxia. PME is a rare, often fatal syndrome, initially responsive to antiepileptic drugs which over time becomes refractory and can be associated with cognitive decline. Linkage analys...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv171
更新日期:2015-08-15 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::Fragile X Syndrome (FXS) is a learning disability seen in individuals who have >200 CGG•CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu006
更新日期:2014-06-01 00:00:00
abstract::Pseudoachondroplasia (PSACH) is one of the more common skeletal dysplasias and results from mutations in cartilage oligomeric matrix protein (COMP). Most COMP mutations identified to date cluster in the TSP3 repeat region of COMP and the mutant protein is retained in the rough endoplasmic reticulum (rER) of chondrocyt...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm155
更新日期:2007-09-01 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::Insulin resistance (IR) is a key determinant of type 2 diabetes (T2D) and other metabolic disorders. This genome-wide association study (GWAS) was designed to shed light on the genetic basis of fasting insulin (FI) and IR in 927 non-diabetic African Americans. 5 396 838 single-nucleotide polymorphisms (SNPs) were test...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds282
更新日期:2012-10-15 00:00:00
abstract::Coronary heart disease (CHD) is the leading cause of death worldwide. Mitochondrial genetic determinant for the development of CHD remains poorly explored. We report there the clinical, genetic, molecular and biochemical characterization of a four-generation Chinese family with maternally inherited CHD. Thirteen of 32...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt256
更新日期:2013-10-15 00:00:00
abstract::Paroxysmal kinesigenic dyskinesia (PKD) is a heterogeneous movement disorder characterized by recurrent dyskinesia attacks triggered by sudden movement. PRRT2 has been identified as the first causative gene of PKD. However, it is only responsible for approximately half of affected individuals, indicating that other lo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx430
更新日期:2018-02-15 00:00:00
abstract::We previously identified Peg1/Mest as a novel paternally expressed gene in the developing mouse embryo. The human PEG1 gene was recently assigned to 7q32 and shown to be imprinted and paternally expressed. Therefore, PEG1 deficiency could participate in the aetiology of pre- and post-natal growth retardation associate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.11.1907
更新日期:1997-10-01 00:00:00
abstract::Recessive mutations in myosin 15, a class XV unconventional myosin, cause profound congenital deafness in humans and both deafness and vestibular dysfunction in mice homozygous for the shaker 2 and shaker 2(J) alleles. The shaker 2 allele is a previously described missense mutation of a highly conserved residue in the...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.12.1729
更新日期:2000-07-22 00:00:00
abstract::Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr501
更新日期:2012-02-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is characterized by airway epithelial damage, bronchoconstriction, parenchymal destruction and mucus hypersecretion. Upon activation by a broad range of stimuli, transient receptor potential vanilloid 4 (TRPV4) functions to control airway epithelial cell volume and epitheli...
journal_title:Human molecular genetics
pub_type: 杂志文章,多中心研究
doi:10.1093/hmg/ddp111
更新日期:2009-06-01 00:00:00
abstract::Inherited defects in the X-chromosomal adrenoleukodystrophy (ALD; ABCD1) gene are the genetic cause of the severe neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). Biochemically the accumulation of very long-chain fatty acids, caused by impaired peroxisomal beta-oxidation, is the pathognomonic characte...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.18.2609
更新日期:2000-11-01 00:00:00
abstract::Xq28 has been of special interest in human genetics because a large number of diseases map to this region. As a step in the molecular analysis of the as yet uncloned disease genes, and as a test for the detailed analysis of larger regions of the genome, we have constructed YAC clone contigs covering the 7.5 Mb region ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.12.2137
更新日期:1994-12-01 00:00:00
abstract::The first 17 amino acids of Huntington's disease (HD) protein, huntingtin, comprise an amphipathic alpha-helical domain that can target huntingtin to the endoplasmic reticulum (ER). N17 is phosphorylated at two serines, shown to be important for disease development in genetic mouse models, and shown to be modified by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds554
更新日期:2013-04-01 00:00:00
abstract::Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Two susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene. Hitherto however, homozygosity for EDNRB mutation...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.3.355
更新日期:1996-03-01 00:00:00
abstract::TMEM70, a 21-kDa protein localized in the inner mitochondrial membrane, has been shown to facilitate the biogenesis of mammalian F1Fo ATP synthase. Mutations of the TMEM70 gene represent the most frequent cause of isolated ATP synthase deficiency resulting in a severe mitochondrial disease presenting as neonatal encep...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw295
更新日期:2016-11-01 00:00:00
abstract::Superovulation or ovarian stimulation is currently an indispensable assisted reproductive technology (ART) for human subfertility/infertility treatment. Recently, increased frequencies of imprinting disorders have been correlated with ARTs. Significantly, for Angelman and Beckwith-Wiedemann Syndromes, patients have be...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp465
更新日期:2010-01-01 00:00:00
abstract::Spinocerebellar ataxia type 2 is an inherited neurodegenerative disorder that is caused by an expanded trinucleotide repeat in the SCA2 gene, encoding a polyglutamine stretch in the gene product ataxin-2. Although evidence has been provided that ataxin-2 is involved in RNA metabolism, the physiological function of ata...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi321
更新日期:2005-10-01 00:00:00
abstract::Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy caused by a polyalanine expansion mutation in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)(6) encodes the first 6 alanines in a homopolymeric stretch of 10 alanines. In most patie...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq559
更新日期:2011-03-15 00:00:00
abstract::The ubiquitin-proteasome system (UPS) is the principal protein degradation system that tags and targets short-lived proteins, as well as damaged or misfolded proteins, for destruction. In spinal and bulbar muscular atrophy (SBMA), the androgen receptor (AR), an Hsp90 client protein, is such a misfolded protein that te...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn419
更新日期:2009-03-01 00:00:00
abstract::Fragile X syndrome, a common cause of intellectual disability and autism, is due to mutational silencing of the FMR1 gene leading to the absence of its gene product, fragile X mental retardation protein (FMRP). FMRP is a selective RNA binding protein owing to two central K-homology domains and a C-terminal arginine-gl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu586
更新日期:2015-03-15 00:00:00
abstract::Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis o...
journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
doi:10.1093/hmg/ddu546
更新日期:2015-03-01 00:00:00
abstract::Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.12.2069
更新日期:1997-11-01 00:00:00
abstract::Degenerate primer pairs that include consensus sequences of evolutionary conserved portions of protein families (BLOCKs or ancient conserved regions) can be used to screen by polymerase chain reaction (PCR) for cognate cDNAs and YACs through much of phylogeny. Nine such primer pairs were developed, and five with sites...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.5.735
更新日期:1994-05-01 00:00:00
abstract::Mutations in Alsin are associated with chronic juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary lateral sclerosis and infantile-onset ascending spastic paralysis. The primary pathology and pathogenic mechanism of the disease remain largely unknown. Here we show that alsin-deficient mice have motor impai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm251
更新日期:2007-12-01 00:00:00
abstract::According to the telomere hypothesis of senescence, the progressive shortening of telomeres that occurs upon division of normal somatic cells eventually leads to cellular senescence. The immortalisation of human cells is associated with the acquisition of a telomere maintenance mechanism which is usually dependent upo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.6.921
更新日期:1997-06-01 00:00:00
abstract::Target genes for the helicase-like transcription factor (HLTF), a member of the SNF/SWI family, were immunoprecipitated from HeLa chromatin fragments with an anti-HLTF antibody. A 182 bp fragment ( HEFT1 ) presented 87% sequence identity with 3.3 kb dispersed repeats from the 4q35 D4Z4 locus linked to facioscapulohume...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.11.1681
更新日期:1998-10-01 00:00:00
abstract::With 46 subunits, human mitochondrial complex I is the largest enzyme of the oxidative phosphorylation system. We have studied the assembly of complex I in cultured human cells. This will provide essential information about the nature of complex I deficiencies and will enhance our understanding of mitochondrial diseas...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh262
更新日期:2004-10-15 00:00:00