Abstract:
:Congenital myopathies (CMs) are a heterogeneous group of muscle diseases characterized by hypotonia, delayed motor skills and muscle weakness with onset during the first years of life. The diagnostic workup of CM is highly dependent on the interpretation of the muscle histology, where typical pathognomonic findings are suggestive of a CM but are not necessarily gene specific. Over 20 loci have been linked to these myopathies, including three exceptionally large genes (TTN, NEB and RYR1), which are a challenge for molecular diagnosis. We developed a new approach using massive parallel sequencing (MPS) technology to simultaneously analyze 20 genes linked to CMs. Assay design was based on the Ion AmpliSeq strategy and sequencing runs were performed on an Ion PGM system. A total of 12 patients were analyzed in this study. Among the 2534 variants detected, 14 pathogenic mutations were successfully identified in the DNM2, NEB, RYR1, SEPN1 and TTN genes. Most of these had not been documented and/or fully characterized, hereby contributing to expand the CM mutational spectrum. The utility of this approach was demonstrated by the identification of mutations in 70% of the patients included in this study, which is relevant for CMs especially considering its wide phenotypic and genetic heterogeneity.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Oliveira J,Gonçalves A,Taipa R,Melo-Pires M,Oliveira ME,Costa JL,Machado JC,Medeiros E,Coelho T,Santos M,Santos R,Sousa Mdoi
10.1038/jhg.2016.2subject
Has Abstractpub_date
2016-06-01 00:00:00pages
497-505issue
6eissn
1434-5161issn
1435-232Xpii
jhg20162journal_volume
61pub_type
杂志文章abstract::Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer p...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.4
更新日期:2016-06-01 00:00:00
abstract::Adrenomedullin (ADM), a peptide characterized by persistent hypotensive activity, is thought to be involved when the control mechanism of blood pressure is deranged, because its plasma concentration is upregulated in hypertensive patients. The receptor for ADM, a molecular complex consisting of calcitonin-receptor-lik...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170100
更新日期:2001-01-01 00:00:00
abstract::Intracellular concentrations of the nucleotide inosine triphosphate (ITP) are regulated by ITP-ase (EC 3.6.1.19), which is encoded by ITPA on chromosome 20p. Subjects with complete deficiency of ITP-ase activity (MIM 147520) have elevated ITP concentrations in erythrocytes, but no obvious clinical abnormalities. Based...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200095
更新日期:2002-01-01 00:00:00
abstract::Genetic studies of neuropsychiatric disorders have often produced conflicting results, which might partly result from the involvement of epigenetic modifications. We intended to explore the possible implication of DNA methylation and human endogenous retroviruses (HERVs) in neuropsychiatric disorders. In the present s...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0081-8
更新日期:2003-01-01 00:00:00
abstract::The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian po...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.99
更新日期:2010-11-01 00:00:00
abstract::Mucolipidosis (ML) III gamma is a rare autosomal-recessive disorder caused by pathogenic mutations in the GNPTG gene. GNPTG encodes the γ-subunit of GlcNAc-1-phosphotransferase that catalyzes mannose 6-phosphate targeting signal synthesis on soluble lysosomal enzymes. ML III gamma patients are characterized by missort...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.13
更新日期:2016-06-01 00:00:00
abstract::L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic disorder characterized essentially by the presence of elevated levels of L-2-hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme involve...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2014.4
更新日期:2014-04-01 00:00:00
abstract::Recently, ubiquitin-specific peptidase 46 (Usp46) has been identified as a quantitative trait gene responsible for immobility in the tail suspension test and forced swimming test in mice. Mice with 3-bp deletion in Usp46 exhibited loss of 'behavioral despair' under inescapable stresses in addition to abnormalities in ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.139
更新日期:2010-03-01 00:00:00
abstract::Southeast Asian ovalocytosis (SAO) is a red blood cell abnormality common in malaria-endemic regions and caused by a 27 nt deletion of the band 3 protein gene. Since band 3 protein, also known as anion exchanger 1, is expressed in renal distal tubules, the incidence of SAO was examined in distal renal tubular acidosis...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0095-2
更新日期:2003-01-01 00:00:00
abstract::The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2014.15
更新日期:2014-05-01 00:00:00
abstract::Diffuse panbronchiolitis (DPB) is a distinctive chronic inflammatory lung disease predominantly found in Asian populations. Although its etiology is unknown, DPB is considered to be a multifactorial disease of whose susceptibility is determined by genetic predisposition unique to Asians. We and others have previously ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050135
更新日期:1999-01-01 00:00:00
abstract::mRNA is an important tool to study the effects of particular mutations on the mode of splicing and transcripts. However, it is often difficult to isolate mRNA because the organ or tissue in which the gene is expressed cannot be sampled. We previously identified two probable splicing mutations (c.6485+5G>A and c.8559-2...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.83
更新日期:2010-10-01 00:00:00
abstract::Factors predisposing to the phenotypic features of familial combined hyperlipidemia have not been clearly defined. In the course of investigating familial coronary artery disease in Utah, we identified a three-generation family in which multiple members were affected with type IIa hyperlipoproteinemia (HLP IIa), type ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050202
更新日期:2000-01-01 00:00:00
abstract::The purpose of the present study was to understand the tissue specificity of DNA methylation and the relationship between methylation and expression of genes with essential roles in neurodevelopment and brain function. We chose dopamine receptor genes (DRD1 and DRD2), NCAM, and COMT as examples of genes with CpG islan...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0382-9
更新日期:2006-01-01 00:00:00
abstract::Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0301-5
更新日期:2005-01-01 00:00:00
abstract::MLXIPL is a transcription factor integral to the regulation of glycolysis and lipogenesis in the liver. Common variants of the MLXIPL gene (MLXIPL) are known to influence plasma triglyceride levels in people of European descent. As MLXIPL has a key role in energy storage, genetic variations of the MLXIPL may be releva...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.109
更新日期:2011-12-01 00:00:00
abstract::The pattern of X-chromosome inactivation (XCI) can affect the clinical severity of X-linked disorders in females. XCI pattern analysis has been conducted mainly by HUMARA assay, a polymerase chain reaction-based assay using a methylation-sensitive restriction enzyme. However, this assay examines the XCI ratio of the a...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0415-1
更新日期:2018-05-01 00:00:00
abstract::The expansion of polyalanine repeats is known to cause at least nine disorders, including congenital central hypoventilation syndrome (CCHS). Unequal crossover has been speculated as the expanding mechanism, in contrast to strand slippage in polyglutamine expansion disorders. We carried out segregation analysis of PHO...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0197-3
更新日期:2007-01-01 00:00:00
abstract::Inborn errors of metabolism can cause epileptic encephalopathies. Biallelic loss-of-function variants in the ITPA gene, encoding inosine triphosphate pyrophosphatase (ITPase), have been reported in epileptic encephalopathies with lack of myelination of the posterior limb of the internal capsule, brainstem tracts, and ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0765-3
更新日期:2020-09-01 00:00:00
abstract::Site-1 protease (S1P) is a subtilisin-related enzyme that cleaves sterol regulatory element-binding proteins (SREBPs) in the lumen of endoplasmic reticulum, thereby initiating the release of transcriptionally active NH2-terminal fragments of SREBPs from membranes. In the experiments reported here, we localized the hum...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380070029
更新日期:2000-01-01 00:00:00
abstract::We constructed a high-density single-nucleotide polymorphism (SNP) map in the 96-kb region containing the DiGeorge syndrome critical region 2 (DGCR2) gene at chromosome 22q11.2, a human counterpart of mouse seizure-related gene SEZ-12. A total of 102 SNPs were isolated from the region by systematic screening among 48 ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170029
更新日期:2001-01-01 00:00:00
abstract::The efficacy of pharmacological chaperone therapy for Fabry disease depends on the type of α-galactosidase A (GLA) mutations. Here, we examined the mutation spectrum of the GLA gene among patients from 115 Japanese families with Fabry disease. Of these, no pathogenic mutations were identified in six families (5.2%). I...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0599-z
更新日期:2019-07-01 00:00:00
abstract::Autosomal dominant cerebellar ataxia (ADCA) is a genetically heterogeneous group of neurodegenerative disorders with overlapping clinical presentation. Recently, a single nucleotide substitution in the 5'-untranslated region (UTR) of the puratrophin-1 (PLEKHG4) gene on chromosome 16q22.1 has been shown to be associate...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0372-y
更新日期:2006-01-01 00:00:00
abstract::Type 2 diabetes mellitus (T2DM) is a group of multifactorial disorders due to either defective insulin secretion or action. Despite the fact that numerous genetic researches of T2DM have been pursued, the pathogenic mechanisms remain obscure. We encountered a T2DM family associated with a balanced reciprocal transloca...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0158-z
更新日期:2004-01-01 00:00:00
abstract::Increased pulse pressure (PP) and decreased mean arterial pressure (MAP) are strong prognostic predictors of adverse cardiovascular events. Recently, the International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS) reported eight loci that influenced PP and MAP. The ICBP-GWAS examined 51 coh...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.31
更新日期:2012-06-01 00:00:00
abstract::The scavenger receptor class B type 1 (SCARB1) gene is a key component in the reverse cholesterol transport pathway and thus plays an important role in lipid metabolism. Studies suggest that the SCARB1 gene may contribute to variation in plasma lipid levels at fasting; however, the results have been inconsistent, and ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-008-0302-2
更新日期:2008-01-01 00:00:00
abstract::Glutathione synthetase deficiency is a rare autosomal recessive disorder resulting in low levels of glutathione and an increased susceptibility to oxidative stress. Patients with glutathione synthetase deficiency typically present in the neonatal period with hemolytic anemia, metabolic acidosis and neurological impair...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.20
更新日期:2016-07-01 00:00:00
abstract::Pyle disease (PYL) is an extremely rare disorder of irregular development of long bone. Recently, homozygous mutations in secreted frizzled-related protein 4 gene (SFRP4) gene were found to underlie this condition. Sequencing of coding regions of SFRP4 gene from an 11-year-old female with PYL was performed. A novel ho...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.166
更新日期:2017-04-01 00:00:00
abstract::The transcriptional factor nuclear factor kappa-beta (NFKB) consists of a multicomponent protein complex that plays a major role in the regulation of many viral and cellular genes. The NFKB complex has two alternative DNA binding subunits. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clon...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050125
更新日期:1999-01-01 00:00:00
abstract::Tuberous sclerosis (TS) is a rare autosomal-dominant genetic disease. TS is manifested by the development of multiple hamartomas, which affect brain, kidneys, retina, skin and other organs. This study aimed to reveal specific features of molecular epidemiology of TS in Russia. Blood DNA samples from 61 patients with d...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0416-0
更新日期:2018-05-01 00:00:00