Abstract:
:Multiminicore disease (MmD) is an autosomal recessive congenital myopathy characterized by the presence of multiple, short core lesions (known as "minicores") in most muscle fibers. MmD is a clinically heterogeneous condition, in which four subgroups have been distinguished. Homozygous RYR1 mutations have been recently identified in the moderate form of MmD with hand involvement. The genes responsible for the three other forms (including the most prevalent phenotype, termed the "classical" phenotype) remained, so far, unknown. To further characterize the genetic basis of MmD, we analyzed a series of 62 patients through a combined positional/candidate-gene approach. On the basis of clinical and morphological data, we suspected a relationship between classical MmD and the selenoprotein N gene (SEPN1), which is located on chromosome 1p36 (RSMD1 locus) and is responsible for the congenital muscular dystrophy with rigid spine syndrome (RSMD). A genomewide screening, followed by the analysis of 1p36 microsatellite markers in 27 informative families with MmD, demonstrated linkage to RSMD1 in eight families. All showed an axial myopathy with scoliosis and respiratory failure, consistent with the most severe end of the classical MmD spectrum; spinal rigidity was evident in some, but not all, patients. We excluded linkage to RSMD1 in 19 families with MmD, including 9 with classical MmD. Screening of SEPN1 in the 8 families that showed linkage and in 14 patients with classical sporadic disease disclosed 9 mutations affecting 17 patients (12 families); 6 were novel mutations, and 3 had been described in patients with RSMD. Analysis of three deltoid biopsy specimens from patients with typical RSMD revealed a wide myopathological variability, ranging from a dystrophic to a congenital myopathy pattern. A variable proportion of minicores was found in all the samples. The present study represents the first identification of a gene responsible for classical MmD, demonstrates its genetic heterogeneity, and reassesses the nosological boundaries between MmD and RSMD.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Ferreiro A,Quijano-Roy S,Pichereau C,Moghadaszadeh B,Goemans N,Bönnemann C,Jungbluth H,Straub V,Villanova M,Leroy JP,Romero NB,Martin JJ,Muntoni F,Voit T,Estournet B,Richard P,Fardeau M,Guicheney Pdoi
10.1086/342719subject
Has Abstractpub_date
2002-10-01 00:00:00pages
739-49issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60361-9journal_volume
71pub_type
杂志文章abstract::A genetic approach is used to ascertain that a single structural locus for triosephosphate isomerase (TPI) (E.C.5.3.1.1.) is expressed in rapidly dividing human lymphoblasts. This approach is made possible through the identification of a rare electrophoretic variant of human TPI. The variant phenotype is expressed by ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress. Similar findings occur in newborns exposed to nicotinergic acetylcholine receptor (AChR) antibodies from myasthenic mothers. We performed linkage studies in families with Escobar syndro...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/506257
更新日期:2006-08-01 00:00:00
abstract::A convenient and reliable method for simulatneous visualization of silver staining (Ag-NOR) of the nucleolus organizers and fluorescent bandings in metaphase chromosomes is described. Studies employing this combined procedure on human chromosomes revealed that the Ag-NOR patterns may be characteristic for each chromos...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::The decreasing cost of whole-genome and whole-exome sequencing has resulted in a renaissance for identifying Mendelian disease mutations, and for the first time it is possible to survey the distribution and characteristics of these mutations in large population samples. We conducted carrier screening for all autosomal...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.08.007
更新日期:2012-10-05 00:00:00
abstract::Ca2+ signaling is vital for various cellular processes including synaptic vesicle exocytosis, muscle contraction, regulation of secretion, gene transcription, and cellular proliferation. The endoplasmic reticulum (ER) is the largest intracellular Ca2+ store, and dysregulation of ER Ca2+ signaling and homeostasis contr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.09.014
更新日期:2018-11-01 00:00:00
abstract::Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301840
更新日期:1998-05-01 00:00:00
abstract::The human genetics community needs robust protocols that enable secure sharing of genomic data from participants in genetic research. Beacons are web servers that answer allele-presence queries--such as "Do you have a genome that has a specific nucleotide (e.g., A) at a specific genomic position (e.g., position 11,272...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.09.010
更新日期:2015-11-05 00:00:00
abstract::Using the technique of in vitro human-hamster fertilization, sperm of four men heterozygous for 4 reciprocal translocations--t(4;17),t(5;13),t(6;7), and t(9;18)--was studied. Frequencies of numerical abnormalities unrelated to the translocations range from 8.3% to 13.3%, and the incidence of imbalances ranges from 23....
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Both sequence variation and copy-number variation (CNV) of the genes encoding receptors for immunoglobulin G (Fcγ receptors) have been genetically and functionally associated with a number of autoimmune diseases. However, the molecular nature and evolutionary context of this variation is unknown. Here, we describe the...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.04.018
更新日期:2012-06-08 00:00:00
abstract::Activating mutations in the genes for fibroblast growth factor receptors 1-3 (FGFR1-3) are responsible for a diverse group of skeletal disorders. In general, mutations in FGFR1 and FGFR2 cause the majority of syndromes involving craniosynostosis, whereas the dwarfing syndromes are largely associated with FGFR3 mutatio...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/427956
更新日期:2005-02-01 00:00:00
abstract::We report here the characterization of a large Chinese family with maternally transmitted aminoglycoside-induced and nonsyndromic deafness. In the absence of aminoglycosides, some matrilineal relatives in this family exhibited late-onset/progressive deafness, with a wide range of severity and age at onset. Notably, th...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/381133
更新日期:2004-01-01 00:00:00
abstract::Centromeric-mapping methods have been used to investigate the association between altered recombination and meiotic nondisjunction in humans. For trisomies, current methods are based on the genotypes from a trisomic offspring and both parents. Because it is sometimes difficult to obtain samples from both parents and b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302799
更新日期:2000-03-01 00:00:00
abstract::Human fetuses with trisomy 21 (T21) have atypical brain development that is apparent sonographically in the second trimester. We hypothesize that by analyzing and integrating dysregulated gene expression and pathways common to humans with Down syndrome (DS) and mouse models we can discover novel targets for prenatal t...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.10.001
更新日期:2020-11-05 00:00:00
abstract::The affected sib-pair method has been used to investigate the mode of inheritance, and to estimate the "disease" allele frequency, for a number of HLA-associated diseases. One of the assumptions of the original sib-pair method is that the disease confers no selective disadvantage on affected individuals. This is obvio...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::We demonstrate that satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes arose in the Hominoidea superfamily. Two groups, distinguished by sequence composition, evolved nonconcurrently, with group 2 evolving 16-23 million years ago (MYA) and the more recent group 1 sequences emerging approx...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/512132
更新日期:2007-03-01 00:00:00
abstract::A mutation in transthyretin (TTR Asn 90) has been identified in the Portuguese and German populations. This variant has a lower pI and was found by screening analyses in 2/4,000 German subjects and in 4/1,200 Portuguese by using either double one-dimensional (D1-D) electrophoresis with isoelectric focusing (IEF) or hy...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::An autosomal recessive deficiency of acid alpha-glucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients--two infants and an adult--provided a rare opportunity to analyze the ef...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Lumbar-disc herniation (LDH), one of the most common musculoskeletal diseases, has strong genetic determinants. Recently, several genes that encode extracellular matrix (ECM) proteins in the intervertebral disc have been reported to associate with LDH. Thrombospondins (THBSs) 1 and 2 are good candidates for the LDH su...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.03.013
更新日期:2008-05-01 00:00:00
abstract::The estimate of heterozygosity and proportion of polymorphic loci for 33 red blood cell loci has been updated by the elimination of some loci of questionable status and the addition of data on 33 loci. The new figures for heterozygosity and proportion of polymorphic loci, .105 and .283, respectively, are based on 60 r...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract::A stepwise logistic-regression procedure is proposed for evaluation of the relative importance of variants at different sites within a small genetic region. By fitting statistical models with main effects, rather than modeling the full haplotype effects, we generate tests, with few degrees of freedom, that are likely ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338007
更新日期:2002-01-01 00:00:00
abstract::Plasma DNA fragmentomics is an emerging area in cell-free DNA diagnostics and research. In murine models, it has been shown that the extracellular DNase, DNASE1L3, plays a role in the fragmentation of plasma DNA. In humans, DNASE1L3 deficiency causes familial monogenic systemic lupus erythematosus with childhood onset...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.09.006
更新日期:2020-11-05 00:00:00
abstract::Mitochondrial DNA (mtDNA) polymorphisms were detected using 13 restriction enzymes on the total DNA obtained from blood samples of five Asian populations: Japanese and Ainu of northern Japan, Korean, Negrito (Aeta) of the Philippines, and Vedda of Sri Lanka. Of a total of 28 restriction-enzyme morphs detected, eight h...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::To determine the receptivity of prenatal care providers and their patients to carrier testing for cystic fibrosis (CF), we offered free carrier screening, followed by genetic counseling of carriers, to all prenatal care providers in Rochester, NY, for all their female patients of reproductive age, pregnant or not. Of ...
journal_title:American journal of human genetics
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::Although balanced translocations are among the most common human chromosomal aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non-Robertsonian translocation. Evidence indicates that de novo formation of the t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of ch...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/507652
更新日期:2006-09-01 00:00:00
abstract::Meckel syndrome (MKS) is a lethal malformation disorder characterized classically by encephalocele, polycystic kidneys, and polydactyly. MKS is also one of the major contributors to syndromic neural tube defects (NTDs). Recent findings have shown primary cilia dysfunction in the molecular background of MKS, indicating...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.05.004
更新日期:2008-06-01 00:00:00
abstract::The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302547
更新日期:1999-09-01 00:00:00
abstract::A population-based study of hemophilia B mutations was conducted in the United Kingdom in order to construct a national confidential database of mutations and pedigrees to be used for the provision of carrier and prenatal diagnoses based on mutation detection. This allowed the direct estimate of overall (micro), male ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302651
更新日期:1999-12-01 00:00:00
abstract::Genetic mapping of complex diseases to date depends on variations inside or close to the genes that perturb their activities. A strong body of evidence suggests that changes in gene expression play a key role in complex diseases and that numerous loci perturb gene expression in trans. The information in trans variants...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.03.022
更新日期:2013-05-02 00:00:00
abstract::Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical a...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2012.03.015
更新日期:2012-05-04 00:00:00
abstract::SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.04.015
更新日期:2020-06-04 00:00:00