Abstract:
:Two brothers presented with a clinical picture characterized by sideroblastic anemia, mild pancreatic insufficiency and progressive muscle weakness. The presence of an associated permanent basal lactic acidemia raised the suspicion of a mitochondrial disease. A muscle biopsy performed in both siblings proved the presence of a significant number of ragged-red fibers, and respiratory chain enzymatic determinations demonstrated a reduced activity of complexes I, III and IV. Mitochondrial DNA studies disclosed the presence of multiple deletions both in skeletal muscle and, to a lesser extent, in leukocytes. Similar, but not identical deletions were also present in the leukocytes and muscle from their mother. Deletions were flanked by short direct repeats. We conclude that such patients suffer from a familial form of mitochondrial disease clinically resembling Pearson's syndrome, with a probably autosomal dominant inheritance.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Casademont J,Barrientos A,Cardellach F,Rötig A,Grau JM,Montoya J,Beltrán B,Cervantes F,Rozman C,Estivill Xdoi
10.1093/hmg/3.11.1945subject
Has Abstract,Author List Incompletepub_date
1994-11-01 00:00:00pages
1945-9issue
11eissn
0964-6906issn
1460-2083journal_volume
3pub_type
杂志文章abstract::Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval conta...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/8.6.989
更新日期:1999-06-01 00:00:00
abstract::Aneuploidy is prevalent in human embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing with maternal age. Superimposed on these meiotic aneuploidies are frequent errors occurring during early mitotic divisions, contributing to widespread chromosomal mosaicism. Here we...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy147
更新日期:2018-07-15 00:00:00
abstract::The apolipoprotein A5 gene (APOA5 ) has been shown to play an important role in determining plasma triglyceride concentrations in humans. We describe here a novel variant, c.553G>T, in the apolipoprotein A5 gene that is associated with hypertriglyceridemia. In contrast to some other polymorphisms, which occur in non-c...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg255
更新日期:2003-10-01 00:00:00
abstract::Filamin B (FLNB) is a cytoplasmic protein that regulates the cytoskeletal network by cross-linking actin, linking cell membrane to the cytoskeleton and regulating intracellular signaling pathways responsible for skeletal development (Stossel, T.P., Condeelis, J., Cooley, L., Hartwig, J.H., Noegel, A., Schleicher, M. a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm114
更新日期:2007-07-15 00:00:00
abstract::Expression of misfolded protein in cultured cells frequently leads to the formation of juxtanuclear inclusions that have been termed 'aggresomes'. Aggresome formation is an active cellular response that involves trafficking of the offending protein along microtubules, reorganization of intermediate filaments and recru...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg074
更新日期:2003-04-01 00:00:00
abstract::CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex det...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx398
更新日期:2018-01-01 00:00:00
abstract::Parental genetic relatedness may lead to adverse health and fitness outcomes in the offspring. However, the degree to which it affects human delivery timing is unknown. We use genotype data from ≃25 000 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study to optimize runs of homozygosity (RO...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa255
更新日期:2020-12-08 00:00:00
abstract::The Smith-Lemli-Opitz syndrome (SLOS; also known as the RSH syndrome) is an autosomal recessive genetic disorder, leading to characteristic multi-organ developmental abnormalities, dysmorphic facies, limb malformations and mental retardation. Mutations in the gene for Delta(7)-dehydrocholesterol reductase (Delta(7)-re...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.9.1385
更新日期:2000-05-22 00:00:00
abstract::Familial infantile myasthenia is an autosomal recessive disorder, recently classified as congenital myasthenic syndrome type Ia. Onset of symptoms is at birth to early childhood with significant myasthenic weakness and possible respiratory distress, followed later in life by symptoms of mild to moderate myasthenia. Th...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.4.635
更新日期:1997-04-01 00:00:00
abstract::Valosin-containing protein (VCP)-associated disease caused by mutations in the VCP gene includes combinations of a phenotypically heterogeneous group of disorders such as hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis. Currently, there are no effe...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt523
更新日期:2014-03-01 00:00:00
abstract::Congenital vertebral malformations (CVMs) are associated with human TBX6 compound inheritance that combines a rare null allele and a common hypomorphic allele at the TBX6 locus. Our previous in vitro evidence suggested that this compound inheritance resulted in a TBX6 gene dosage of less than haploinsufficiency (i.e. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy358
更新日期:2019-02-15 00:00:00
abstract::Reduced activity of beta4-galactosyltransferase 7 (beta4GalT-7), an enzyme involved in synthesizing the glycosaminoglycan linkage region of proteoglycans, is associated with the progeroid form of Ehlers-Danlos syndrome (EDS). In the invertebrates Drosophila melanogaster and Caenorhabditis elegans, mutations in beta4Ga...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm372
更新日期:2008-04-01 00:00:00
abstract::Missense mutations and extra copies of the alpha-Synuclein gene result in Parkinson disease (PD). Human stem and progenitor cells can be expanded from embryonic tissues and provide a source of non-transformed neural cells to explore the effects of these pathogenic mutations specifically in human nervous tissue. We ove...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm008
更新日期:2007-03-15 00:00:00
abstract::Recent prospective analysis identified secretory phospholipase A(2)-IIa (sPLA(2)IIa) as a coronary artery disease (CAD) risk predictor. This study aimed to examine the relationship between serum levels of sPLA(2)IIa and variation in the sPLA(2)IIa gene (PLA2G2A) in a cohort of patients with Type II diabetes (T2D) mell...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi453
更新日期:2006-01-15 00:00:00
abstract::Lung cancer demonstrates the highest mortality in the UK. Previous studies have implicated allelic loss at chromosome 17q in the development of non-small cell lung carcinoma (NSCLC), and a number of known and putative tumour-suppressor genes reside within this region. One candidate tumour-suppressor gene is cytoglobin...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl128
更新日期:2006-07-01 00:00:00
abstract::The DUX4 transcription factor is normally expressed in the cleavage-stage embryo and regulates genes involved in embryonic genome activation. Misexpression of DUX4 in skeletal muscle, however, is toxic and causes facioscapulohumeral muscular dystrophy (FSHD). We recently showed DUX4-induced toxicity is due, in part, t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz242
更新日期:2019-12-01 00:00:00
abstract::The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineag...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr069
更新日期:2011-05-15 00:00:00
abstract::Genetic analysis of mouse mutants has demonstrated the importance of the homeobox genes Rpx, Lhx3 and Pit1 for anterior pituitary gland development. Pit1 mutations have also been identified in several human families with multiple pituitary hormone deficiencies. To identify additional homeobox regulators of pituitary d...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.3.457
更新日期:1997-03-01 00:00:00
abstract::The X-linked reproductive homeobox (RHOX) gene cluster encodes transcription factors preferentially expressed in reproductive tissues. This gene cluster has important roles in male fertility based on phenotypic defects of Rhox-mutant mice and the finding that aberrant RHOX promoter methylation is strongly associated w...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw313
更新日期:2016-11-15 00:00:00
abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz094
更新日期:2019-08-15 00:00:00
abstract::Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought to confer toxic properties on the disease proteins through alt...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg144
更新日期:2003-06-01 00:00:00
abstract::NPHP4 mutations cause nephronophthisis, an autosomal recessive cystic kidney disease associated with renal fibrosis and kidney failure. The NPHP4 gene product nephrocystin-4 interacts with other nephrocystins, cytoskeletal and ciliary proteins; however, the molecular and cellular functions of nephrocystin-4 have remai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr214
更新日期:2011-08-15 00:00:00
abstract::Obesity is a major public health problem with strong genetic determination; however, the genetic factors underlying obesity are largely unknown. In this study, we performed a genome-wide association scan for obesity by examining approximately 500 000 single-nucleotide polymorphisms (SNPs) in a sample of 1000 unrelated...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn072
更新日期:2008-06-15 00:00:00
abstract::Andersen's syndrome (AS) is a rare and dominantly inherited pathology, linked to the inwardly rectifying potassium channel Kir2.1. AS patients exhibit a triad of symptoms that include periodic paralysis, cardiac dysrhythmia and bone malformations. Some progress has been made in understanding the contribution of the Ki...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu462
更新日期:2015-01-15 00:00:00
abstract::The breast cancer gene, BRCA2, is essential for viability, yet patients with Fanconi anemia-D1 subtype are born alive with biallelic mutations in this gene. The hypomorphic nature of the mutations is believed to support viability, but this is not always apparent. One such mutation is IVS7+2T>G, which causes premature ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw066
更新日期:2016-05-15 00:00:00
abstract::Mutations in the gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase (PDE6C) have been recently reported in patients with autosomal recessive inherited achromatopsia (ACHM) and early-onset cone photoreceptor dysfunction. Here we present the results of a comprehensive study on PDE6C mutation...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq517
更新日期:2011-02-15 00:00:00
abstract::Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected s...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds477
更新日期:2013-02-15 00:00:00
abstract::A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha-synuclein gene were amplified by PCR from i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.4.751
更新日期:1998-04-01 00:00:00
abstract::Mutations in RP2 cause the second most frequent form of X-linked retinitis pigmentosa, a severe retinal degeneration that leads to loss of visual acuity and blindness. The RP2 gene encodes a protein with homology to cofactor C, a tubulin-folding chaperone. By searching protein sequence databases, we identified a whole...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.11.1177
更新日期:2001-05-15 00:00:00
abstract::Polyglutamine expansion in certain proteins causes neurodegeneration in inherited disorders such as Huntington disease and X-linked spinobulbar muscular atrophy. Polyglutamine tracts promote protein aggregation in vitro and in vivo with a strict length-dependence that strongly implicates alternative protein folding an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl135
更新日期:2006-07-01 00:00:00