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 androgen receptor gene at the genomic DNA level and does not reflect the ratio of either targeted gene directly or at the mRNA level. Here, we report four females with Dent disease, and we clarified the correlation between XCI and female cases of Dent disease using not only HUMARA assay but also a novel analytical method by RNA sequencing. We constructed genetic analysis for 4 female cases showing high level of urinary low-molecular-weight proteinuria and their parents. Their XCI pattern was analyzed by both HUMARA assay and an ultra-deep targeted RNA sequencing of the CLCN5 gene using genomic DNA and mRNA extracted from both leukocytes and urine sediment. All four cases possessed pathogenic variants of the CLCN5 gene. XCI analysis revealed skewed XCI in only two cases, while the other two showed random XCI. All assay results of HUMARA and targeted RNA sequencing in both leukocytes and urinary sediment were clearly identical in all four cases. We developed a novel XCI analytical assay of ultra-deep targeted RNA sequencing and revealed that skewed XCI explains the mechanism of onset of female Dent disease in only half of such cases.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Minamikawa S,Nozu K,Nozu Y,Yamamura T,Taniguchi-Ikeda M,Nakanishi K,Fujimura J,Horinouchi T,Shima Y,Nakanishi K,Hattori M,Kanda K,Tanaka R,Morisada N,Nagano C,Sakakibara N,Nagase H,Morioka I,Kaito H,Iijima Kdoi
10.1038/s10038-018-0415-1subject
Has Abstractpub_date
2018-05-01 00:00:00pages
589-595issue
5eissn
1434-5161issn
1435-232Xpii
10.1038/s10038-018-0415-1journal_volume
63pub_type
杂志文章abstract::Mature-onset diabetes of the young, type 2 (MODY2) is associated with mutations in the glucokinase (GCK) gene that result in impaired glucokinase activity. Although more than 200 inactivating GCK mutations have been reported, only less than 20% of these mutations have been functionally characterized. In this work, we ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-008-0271-5
更新日期:2008-01-01 00:00:00
abstract::In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recomb...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2016.46
更新日期:2016-08-01 00:00:00
abstract::Fucosidosis is a rare lysosomal storage disease caused by a defect of the alpha-L: -fucosidase (FUCA1) gene. Worldwide 26 mutations underlying the disease have been reported. By direct DNA sequencing of exons and flanking introns, homozygous Y126X mutation and Q281R polymorphism were found in a Taiwanese patient with ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0136-3
更新日期:2007-01-01 00:00:00
abstract::In this study, the structure of the alpha1-acid glycoprotein (AGP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORMI*S a...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170023
更新日期:2001-01-01 00:00:00
abstract::X-linked inheritance is very rare and is estimated to account for only 1-5% of all nonsyndromic hearing loss cases. We found a multiplex family from China segregating with X-linked nonsyndromic hearing loss. After exclusive analysis of 10 common variations of three hearing loss-related genes, GJB2, mtDNA12srRNA and SL...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-018-0443-x
更新日期:2018-06-01 00:00:00
abstract::Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor (PAF) acetylhydrolase (PAF-AH), is a member of the serine-dependent class of A2 phospholipases that hydrolyze sn2-ester bonds of fragmented or oxidized phospholipids at sites where atherosclerotic plaques are forming. Mo...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0151-6
更新日期:2004-01-01 00:00:00
abstract::Lafora disease (LD) is a rare autosomal recessive genetic disorder characterized by epilepsy, myoclonus, and progressive neurological deterioration. LD is caused by mutations in the EMP2A gene encoding a protein phosphatase. A second gene for LD, termed NHLRC1 and encoding a putative E3 ubiquitin ligase, was recently ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0263-7
更新日期:2005-01-01 00:00:00
abstract::GATA zinc finger domain-containing 2B (GATAD2B) is a subunit of the methyl-CpG-binding protein-1 complex (MECP1), which deacetylates methylated nucleosomes and regresses transcriptional activity. Recently, GATAD2B has been elucidated as a candidate gene in patients with intellectual disability (ID). In this study, we ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.164
更新日期:2017-04-01 00:00:00
abstract::Genomic imprinting is an epigenetic phenomenon that leads to parent-specific differential expression of a subset of genes. Most imprinted genes form clusters, or imprinting domains, and are regulated by imprinting control regions. As imprinted genes have an important role in growth and development, aberrant expression...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2013.51
更新日期:2013-07-01 00:00:00
abstract::Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 that were associated with coronary artery disease (CAD) and myocardial infarction (MI) in Caucasian populations from northern Europe and North America...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0230-6
更新日期:2008-01-01 00:00:00
abstract::Fabry disease is a genetic disorder caused by a deficiency of α-galactosidase A (GLA). In our previous studies, we structurally investigated Fabry disease using a structural analysis system, and revealed that structural changes in GLA are very important for understanding the molecular basis of this disease. To the bes...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.31
更新日期:2011-06-01 00:00:00
abstract::Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0809-8
更新日期:2020-10-09 00:00:00
abstract::The gene for Clara cell secretory protein (CC16) is an ideal candidate for investigating genetic predisposition to asthma because of its role in the airway as an anti-inflammatory molecule, differences in its levels between asthmatics and healthy controls, and its genetic location (11q13). We investigated the associat...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0206-8
更新日期:2004-01-01 00:00:00
abstract::The identification of anticipation in schizophrenia is a recent focus in the genetic epidemiology of schizophrenia, although it involves some controversial methodological issues. We explored the evidence of anticipation among 44 Japanese two-generation pairs with schizophrenia found by reviewing nine years of admissio...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050076
更新日期:1998-01-01 00:00:00
abstract::Multiple pterygium syndrome (MPS) is an autosomal recessively inherited condition that becomes evident before birth, with pterygium at multiple joints and akinesia. There are two forms of this syndrome that are differentiated by clinical severity: the milder form, Escobar type (OMIM#265000), and the more severe form, ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.2
更新日期:2015-04-01 00:00:00
abstract::The INPPL1 (inositol polyphosphate phosphatase-like 1) gene encodes the inositol phosphatase, SHIP2 (for src homology 2 domain-containing inositol phosphatase 2). SHIP2 functions to dephosphorylate, and negatively regulate, the lipid second messenger phosphatidylinositol (3,4,5)P3. SHIP2 has been well studied in the a...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2016.119
更新日期:2017-02-01 00:00:00
abstract::We present a 3⅓-year-old girl with severe Charcot-Marie-Tooth disease type 1 (Dejerine-Sottas disease), who was a compound heterozygote carrying a deletion of the whole peripheral myelin protein 22 (PMP22) and a deletion of exon 5 in the other PMP22 allele. Haplotype analyses and sequence determination revealed a 11.2...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2010.106
更新日期:2010-11-01 00:00:00
abstract::Human minisatellite B6.7 shows extensive allele length and structural variability in north Europeans. We analysed this locus in the Japanese population. Allele size distributions showed that Japanese retain extensive allele length variability but have significantly smaller alleles compared with north Europeans. In con...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200031
更新日期:2002-01-01 00:00:00
abstract::Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase ( MTHFR) gene is a risk factor for neural tube defects (NTDs) in many populations, including Italians. Another common mutation on the MTHFR gene, A1298C, has also been described as a risk mutation. Furthermore, several studies have suggeste...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200043
更新日期:2002-01-01 00:00:00
abstract::Partner and localiser of BRCA2 forms part of a macromolecular complex with BRCA1 and BRCA2, which is critical for the repair of double-strand DNA breaks by homologous DNA recombination. Germline loss-of-function variants in the PALB2 gene may confer an increased lifetime risk of breast, pancreatic, ovarian and other c...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0680-7
更新日期:2020-01-01 00:00:00
abstract::Tandem mass screening has recently been started in Japan, but genetic screening has yet to be widely performed in neonates and many unexpected deaths are still being reported. We previously reported two cases of sudden infant death that may have been prevented had newborn screening been performed. In this study, we re...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2017.79
更新日期:2017-11-01 00:00:00
abstract::Heterozygous pathogenic variants in SLC12A2 are reported in patients with nonsyndromic hearing loss. Recently, homozygous loss-of-function variants have been reported in two patients with syndromic intellectual disability, with or without hearing loss. However, the clinical and molecular spectrum of SLC12A2 disease ha...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-021-00904-2
更新日期:2021-01-27 00:00:00
abstract::As a result of the combination of great linguistic and cultural diversity, the highland populations of Daghestan present an excellent opportunity to test the hypothesis of language-gene coevolution at a fine geographic scale. However, previous genetic studies generally have been restricted to uniparental markers and h...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2015.132
更新日期:2016-03-01 00:00:00
abstract::The use of novel sequencing and high-throughput techniques has become widespread, and are now readily available to obtain the comprehensive transcription profile of the human genome. Noncoding RNAs (ncRNAs) are transcripts that have no apparent protein-coding capacity, but they have important roles in human physiology...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2016.66
更新日期:2017-01-01 00:00:00
abstract::Leptin, a possible mediator between energy homeostasis, inflammation and cardiovascular disease (CVD), acts via leptin receptors. We investigated association of single-nucleotide polymorphisms (SNPs) and haplotypes of the leptin receptor gene (LEPR) with several CVD risk factors: body mass index, waist circumference (...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2014.82
更新日期:2014-11-01 00:00:00
abstract::Genetic testing for BRCA1/2 mutations has become the standard clinical practice. Recent findings suggest the clinical significance of multigene panel testing of BRCA1/2 and other cancer-related genes. However, the clinical features of patients with breast cancer with germline mutations identified using multigene panel...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0729-7
更新日期:2020-07-01 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::Most studies on the genetic basis of human skin pigmentation have focused on people of European ancestry and only a few studies have focused on Asian populations. We investigated the association of skin reflectance and freckling with genetic variants of melanocortin 1 receptor (MC1R) gene in Japanese. DNA samples were...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.96
更新日期:2012-11-26 00:00:00
abstract::Since adducin modulates cellular sodium retention, its follows that ADD1, which encodes the alpha-subunit of adducin, is an attractive candidate gene for blood pressure variation. Association studies examining the relationship between polymorphism at ADD1 codon 460 (G460W) and both hypertension and blood pressure, whi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050148
更新日期:1999-01-01 00:00:00
abstract::A hypercholesterolemic patient medicated with cerivastatin for 22 days resulted in acute rhabdomyolysis. CYP2C8 and CYP3A4 are the major enzymes responsible for the metabolism of cerivastatin, and a transporter, OATP2, contributes to uptake of cerivastatin to the liver. In this study, the patient's DNA was sequenced i...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0188-6
更新日期:2004-01-01 00:00:00